New Precision Determination of g_p and G_F the MuXperiments at PSI
重庆市第一中学校2024-2025学年高三上学期12月月考英语试题

重庆市第一中学校2024-2025学年高三上学期12月月考英语试题学校:___________姓名:___________班级:___________考号:___________一、阅读理解A Silk Road Oasis (绿洲): Life in Ancient DunhuangNamed “Blazing Beacon” after the watchtowers along its walls, Dunhuang was once a vital meeting point at the gateway to China. The routes that joined here ran through Constantinople in the West and Japan in the East. But there was more to this blooming oasis than trade. For over 1000 years, Dunhuang was also an important religious site, a cultural melting pot where ideas, technologies and art flowed freely.This exhibition provides a rare glimpse into the ordinary lives of people long ago through the remarkable contents of the Library Cave, the documents include personal letters and wills concerning multiple languages, faiths and cultures including Buddhism, Zoroastrianism, Manichaeism and Christianity; and span topics as diverse as literature, astronomy, medicine, politics and art.Exhibition Highlights:The Diamond Sutra (868 CE): The oldest complete printed book with a date, significant in Mahayana Buddhism in East Asia.Dunhuang Star Chart: The earliest known map of the night sky from any culture, showing early astronomical knowledge.Old Tibetan Annals: Tibetan, detailing the Tibetan empire from 641 to 764.9th-century Zoroastrian script piece: A rare text about Zoroaster, nearly 400 years earlier than other known Zoroastrian texts.Ticket PricingBritish Library Members can go free. Other reduced prices are available, including for under 18s and those with a disability. The British Library also offers discounts for groups of 10+. Please see the ticket options for more details and select the ticket type you require.1.Which can be found at the exhibition?A.Documents from 900 years ago.B.Detailed studies on Buddhist teachings.C.Modern understanding of the Silk Road.D.Extraordinary drafts, documents, and artworks.2.What is one of the exhibition highlights?A.A modern map of stars.B.A written material about Zoroaster.C.The oldest complete handwritten book with a date.D.The earliest history textbook used in Tibet.3.Who can get a discount at the exhibition?A.A group of 8 adults.B.Foreign visitors out of the UK.C.A 13-year-old middle school student.D.A friend of a British Library Member.As the first-ever Chinese captain to compete in the Vendee Globe, known as one of the world’s toughest endurance challenges, Olonne on Sunday in the 10th edition of the legendary solo, non-stop, around-the-world yacht race.Born in Pingdu, north China’s Shandong Province, Xu encountered two life-changing events at the age of 12 — seeing the sea for the first time and losing his lower left arm due to a fireworks accident. “Losing my arm taught me perseverance, and from then on, I wanted to push my own limits. Discovering the sea opened a new path for me,” Xu said.Always athletic, he first excelled in track and field before discovering a lifelong passion for sailing. His talent and determination led him to represent China in sailing at the 2008 Beijing Paralympics. “Sailing isn’t just about competing; it’s about constantly learning and exploring the sea,” he explained.Over time, Xu gained recognition both in Route du Rhum transatlantic solo race and went on to complete China’s first double-hulled circumnavigation. Now, his participation in the Vendee Globe marks a historic milestone as he becomes the first Chinese sailor to compete in a field traditionally dominated by European captains.“Being the first Chinese sailor here is more than a personal achievement. It’s about inspiring others to see beyond obstacles and to explore what’s possible,” Xu said. Asked about his goal in this year’s race, Xu emphasized the importance I’ll aim to place in the middle of the pack,” he stated confidently.4.Why did Xu Jingkun pursue a career in sailing?A.He wanted to use his athletic background.B.He hoped to win the Vendee Globe race.C.He aimed to compete with excellent European sailors.D.He was influenced by his injury and seeing the sea.5.What is one of Xu Jingkun’s major achievements?A.Winning the Route du Rhum transatlantic race.B.Competing in the first Vendee Globe race.C.Representing China at the Paris Olympics.D.Completing China’s first double-hulled circumnavigation.6.Which of the following best describes Xu Jingkun’s character?A.Ambitious and generous.B.Strong-willed and exploratory.C.Creative and hard-working.D.Cautious and conservative.7.What is the best title for this passage?A.A Chinese Sailor’s Inspiring JourneyB.Breaking Records in Chinese SailingC.A New Path to V endee Globe RaceD.Overcoming Physical Limitations in SportsA recent study examined how online images strengthen gender bias (偏见), even when written descriptions are more balanced. Researchers, led by Douglas Guilbeault, explored how gender bias is conveyed in images versus text and its impact on users. (like doctor or nurse) or social roles (like neighbor or friend).The study analyzed nearly 350,000 Google Images showing men and women in various jobs and roles, then compared these to billions of words from in text. Both images and text showed biased associations, with women more often described in liberal arts roles and men inscience and technology. However, the imbalance was “statistically more extreme” in images. For example, all images of software developers were male, while text descriptions included women. Compared to real-world workforce data, images overrepresented men, while text more often overrepresented women.Researchers had volunteers search for 22 occupation. The study found that viewing images rather than text intensified participants’ gender biases, which persisted for days afterward.A potential explanation is the complex algorithms (算法) that run search engines like Google Images. “Consistently, we find that the algorithm appears to be privileging male content.” The site may be holding a mirror to users’ attitude. “Google is just a system,” he says, “reflecting what’s going on in other areas of the internet.” Also, images affect us differently than text. Images are particularly sticky in our mind, known as the picture-superiority effect, and more easily processed, remembered, and emotionally stirring than text.As society shifts toward visual communication, Guilbeault warns that images, being a potent vehicle for stereotypes (刻板印象), may deepen biases unless new cultural rules intervene. 8.What did the researchers discover in the study?A.The jobs taken by men and women were imbalanced.B.Images showed a more extreme bias than text.C.Men were doing a better job than women in images.D.Gender bias in text had a greater influence on readers.9.How did the researchers study the gender bias of online images?A.By examining a specific case of gender discrimination online.B.By interviewing people about their views of gender in professions.C.By experimenting on participants’ reactions to different professions.D.By analyzing the gender associations in online images and text data.10.What can be inferred from Guilbeault’s words?A.Images contain more detailed information than text.B.The result reflects people’s biases in real life.C.The engineers writing the algorithms are biased.D.People prefer images to written descriptions.11.What is the author’s possible purpose in writing the text?A.To help realize how online images deepen gender bias.B.To analyze the effects of gender stereotypes in modern society.C.To propose solutions for discrimination in search engine algorithms.D.To prove Google Images’ gender inequality.A substance found in a fungus (真菌) that commonly disables and kills insects has been shown to block pathways critical for the growth of some cancers. Building on previous research, researchers from the University of Nottingham in the UK looked into the cancer-fighting abilities of cordycepin, a chemical produced by parasitic Cordyceps and Ophiocordyceps species (冬虫夏草真菌) to assist their infection of a living host’s body, often affecting the insect’s behavior before killing them.Advances in scientific techniques enabled cell signaling pathways, and protein production across a vast number of cells in order to figure out what cordycepin is doing. “It has become easier and less expensive to do these very large experiments, so we were able to examine thousands of genes at the same time,” says RNA biologist Cornelia de Moor.Through lab experiments on human tissue cultures and a genetic analysis of how cordycepin worked on these cells, the team found the chemical was transformed into a more active substance called cordycepin triphosphate, which is responsible for slowing down cell activity.The researchers found pathways often controlled by cancer cells to assist their spread throughout the human body. Although it’s not clear yet which molecules (分子) cordycepin triphosphate is targeting, the team did find that the chemical appeared to be working quickly.Further research is required to turn the findings into new cancer treatments, yet understanding how the molecule affects cell growth could set the foundations for new types of cancer drugs. Importantly, the precision with which cordycepin triphosphate operates means that it could overcome the challenge faced by many current treatments: trying to take our cancer cells without causing too much damage to healthy tissue.12.What does the underlined word in paragraph 1 most likely mean?A.dependent B.protective C.beneficial D.weak13.Which of the following best summarizes the role of cordycepin?A.It produces protein in a cheap and effective way.B.It enhances the signaling pathways for cancer cells.C.It directly works on cancer cells to slow down their activities.D.It turns into a substance that blocks signaling pathways.14.What may researchers focus on in the future?A.Identifying the precise targeted molecules.B.Finding cheaper ways to produce cordycepin.C.Testing cordycepin triphosphate on insects.D.Studying how cancer cells damage healthy tissues.15.What’s the main idea of the passage?A.A fungus’s substance was discovered to influence insects’ behavior.B.Researchers are using new technology to study gene expression.C.A substance from a fungus shows potential for cancer treatment.D.Scientists are developing a new drug that cures cancer with no side effects.Worrying is just a familiar emotion that a person gets when he starts to get concerned about the outcome of something that he cares about. 16 It’s all about the triggers (诱因).Once a person comes across a trigger that reminds him of something he cares about, he might start worrying about that thing. Fears then fuel the person’s thoughts and so he starts imaging possible negative situations. 17 When a person gives in to the first negative thought, a series of issues emerge. He starts looking for more evidence to calm himself down. When that happens the person becomes more likely to come across a new trigger that leads to more worrying. 18 In other words there might be no way to find a piece of data that calms the person down during that specific phase of his life.19 As you might have already guessed, not giving in to the first negative thought is one of the best strategies to deal with worrying. By pushing that negative thought away as soon as it appears you can give yourself the chance not to fall into this worrying trap.But it’s important to note that worrying can also be useful if it motivates you to take action to change things or to find real data that can help you. 20 But if you already took the exam and you are now worried worrying in such a case is a total waste of time and that it might just lead to more worrying.So as soon as you make sure you really can’t change anything at the moment, just push the first negative thought away gently and remind yourself that worrying will just open the door to more negative thinking.A.More worrying means more time wasted.B.This is where the downward cycle often begins.C.But what we may not know is its negative effects.D.But do you know how the worrying process starts?E.However, there are still ways to break free from this cycle.F.You may study harder if worried about, for example, an upcoming exam.G.The biggest problem here is that things people worry about are usually uncertain.二、完形填空In Philadelphia on a Thursday in July, 52-year-old Christine King was hurrying to her job. Or trying to. The traffic on the road was 21 , — no surprise for this stretch of highway at rush hour. When she pulled into the exit lane, she noticed a man and woman beside a stopped vehicle in a/an 22 . The woman tried to 23 the man as he moved towards the guard-rail (护栏) overlooking a 40-foot drop with something in his arms. Then he 24 to throw it over the rail. The woman struggled to pull the man back from the 25 .It was when King realized it was a 26 in his arms. She hurried out of the car and dashed to the man at the risk of being pushed off the rail. Again and again she grasped it but could not 27 it. Then the sound of sirens — a policeman arrived his weapon drawn. Though panicky, the man had not yet done the 28 , but one wrong word or movement could push him to extremes. The next thing King knew was that the officer was on the man, grabbing his arm. This was the moment when all would be 29 — either he would throw his little girl over the rail in a final act, or someone would get their hands on the child first. In the chaos, King 30 to get the terrified baby back.Through sobs, her mother 31 what had happened: a breakup, a new apartment and an attempted fresh start. Then the man had found them and forced them into the car. How they 32 there on the bridge wasn’t quite clear. But they were safe now. The man was later proved33 and would be sentenced to up to 23 months in prison.Many have wondered at King’ s 34 . As a mother of five, she said a baby’s life was at risk and that was 35 enough.21.A.thick B.thin C.light D.smooth 22.A.hurry B.argument C.conversation D.chat 23.A.push B.ignore C.anger D.block 24.A.pretended B.begged C.threatened D.agreed 25.A.top B.center C.edge D.corner 26.A.doll B.package C.baby D.weapon 27.A.approach B.catch C.place D.free 28.A.uncertain B.unthinkable C.unrealistic D.unpleasant 29.A.resolved B.complicated C.started D.messed 30.A.attempted B.managed C.failed D.hoped 31.A.delivered B.disbelieved C.regretted D.inferred 32.A.ended up B.broke away C.came across D.made up 33.A.risky B.rude C.guilty D.innocent 34.A.loyalty B.bravery C.strength D.wisdom 35.A.courage B.trouble C.reason D.time三、语法填空阅读下面短文,在空白处填入1个适当的单词或括号内单词的正确形式。
全新版大学英语综合教程(第二版)课后答案unit1-unit8

Key to Exercises (unit 1)V ocabulary:I. 1). respectable 2) .agony 3). put down 4). sequence 4). rigid 5). hold back 6). distribute 7). off and on 8). vivid9). associate 10). finally 11). turn in 12). tackle2. 1) has been assign ed to the newspaper’s Paris office2) was so extraordinary that I didn’t know whether to believe him or not3) a clear image of how she would look in twenty years’ time4) gave the command the soldiers opened fire5) buying bikes we’ll keep turning them out3. 1) reputation/rigid / to inspire 2) and tedious / what’s more / out of date ideas3) compose / career / avoid showing / hardly hold backII. 1). composed 2). severe 3) agony 4). extraordinary5). recall 6). command7). was violating 8). anticipateIII. 1. at 2. for 3. of 4. with5. as6. about7. to8. in9. from 10. on/uponComprehensive Exercises(A)(1) hold back (2) tedious (3) scanned (4) recall(5) vivid (6) off and on (7) turn out/in (8) career(B)(1) last (2) surprise (3) pulled (4) blowing (5) dressed (6) scene(7) extraordinary (8)image (9)turn (11) excitementII. Translation1) As it was a formal dinner party, I wore formal dress, as Mother told me to.2) His girlfriend advised him to get rid of /get out of his bad habit of smoking before it took hold.3) Anticipating that the demand for electricity will be high during the next few months, they have decided to increase its production.4) It is said that Bill has been fired for continually violating the company’s safety rules./Bill is said to have been fired for continually violating the company’s safety rules.5) It is reported that government has taken proper measures to avoid the possibility of a severe water shortage./The local government is reported to have taken proper measures to avoid the possibility of a severe water shortage.2.Susan lost her legs because of/in a car accident. For a time, she didn’t know how to face up to the fact that she would never be able to walk again.One day, while scanning (through)some magazines, a true story caught her eye/she was attracted by a true story. It gave a vivid description of how a disabled girl became a writer. Greatly inspired, Susan began to feel that she , too, would finally be able to lead a useful life.Key to exercises Unit 2I.V ocabulary :1. 1) absolutely 2) available 3) every now and then4) are urging/ urged 5) destination6) mostly 7) hangs out 8) right away 9) reunion10)or something 11)estimate12) going ahead2.1) It seemed that his failure in the examination was still on his mind.2) He was completely chocked up by the sight of his team losing in the final minutes of the game.3) She was so lost in study that she forgot to have dinner.4) Something has come up and I am afraid i won't be able to accomplish the project on time.5) The cost of equipping the new hospital was estimated at $2 million.3.1) were postponed ... the awful ...is estimated2) reference ... not available ... am kind of3) not much of a teacher... skips...go headII.1.to;2. for;3. at;4. from;5. in;6. to;7. on;8.withIII.1). more or less; 2). kind of/ sort of3). Something 4). kind of/ sort of5). more or less 6). or somethingComprehensive Exercises:I. (A) 1) choked up 2) awful 3) practically 4) neighborhood5) correspondence 6) available 7) destination8) reunion 9) Mostly 10)postponing 11) absolutely(B) 1) how 2)savings 3) embarrassment 4) phone 5)interrupted6)touch 7)envelope 8) signed 9) message10) neededII. Translation1.1) Half an hour had gone by, but the last bus hadn’t come yet. We had to walk home.22) Mary loo ks as if she is very worried about the Chinese exam because she hasn’t learned the texts by heart.3) Since the basketball match has been postponed, we might as well visit the museum.4) He stayed in Australia with his parents all the way through World War II.5) Since I graduated from nanjing University in 1985, I have kind of lost touch with my classmates.2. It is not easy to keep in touch with friends when they are far away. This is certainly true in my case.It has been a couple of years since I left my old meighborhood and all the friends I had there. I've been meaning to write to them but something or other comes up and I just don't seem to find the time. They are always on my mind, however, and I think I will certainly make an effort to keep up correspondence with them in future.Key to Unit 3:V ocabulary:I:1) brief 2) in terms of 3) cut…off 4) tend 5) anyway6) precise 7)in the form of8) initiative 9) convey 10) in two minds 11)concept 12)grasp1.1) …has ensured their team a place in the Cup Final.2) ….medical workers’ responsibility to heal the wounded and rescure the dying.3)…..entertain as well as educate the learner.4) ….can do without air and water.5)… is likely to be held in June2.1) lies in ….contact between2) basis of ….is likely….sufficient ….at the moment3) the steady ….ensures…will be highlyII.1. regained2. undecided3. undersupplied4. disabled….5. precondition6. foresight7. mispronounced8. enrichIII.1.略2.1) majority 2) accepted 3) increased 4) weakness 5) local/regional6) late 7) wrong 8) falseComprehensive Exercises:I.Cloze(A)1) highly; 2) bring about 3) evident 4)rate 5) sufficient; 6) put across 7) proportion 8) Hence,9) ensure..p ut across;…proportion; ….Hence;….ensure;….audience…(B)1)understand 2) tracel 3) practical 4) use 5) Another 6) likely 7) affect 8) developments 9)supply 10) SomedayII.Translation:1.1) As is predicted by scientists, global pollution has become one of the most serious problems humans are faced with.2) Competition for these jobs is very tough ---- we have five times as many applicants this year as we did last year/there are five times as many applicants this year as there were last year.3) As the facts show, educational programs need to fit into the national plan for economic development.4) The car burns too much gas, and moreover, the price is almost twice as much as I intend to pay.5) To understand a great international event, we, first of all, need to consider the historical and political background to it.2.It is hard to imagine how our forefathers could do without so many conveniences that modern technology has brought about. Back then only a small proportion of the population enjoyed the comforts of life. The majority didn’t even have sufficient food, not to speak of/ let alone the privilege of being educated. However, many people blame modern technology for creating so many problems. They want to slow down the rate of progress. But no one can put the clock back.UNIT 4nguage sense enhancement.passed away grew in stature proud route values and principle above all bottom tiny giant balance sheets2.V ocabulary.wreck balance approaching handle discard Above all diet do with checked on clean up weekly principle3.Rewrite sentences.<1> to look for survivors were abandoned after it had been/was determined that all the peoplein the sunken ship had died.<2> was amazed that bob left a well-paid job to travel around the world.<3> for a loan has been turned down by many a bank as her business is small and she couldprovide no guarantee.<4>express her thoughts with precision, so people often misunderstand her.<5> will weaken our determination to modernize our country in the shortest possible time.plete the sentences.4for sale hunting for be amazed bybecome skilled handle their loanscharacter by calling on he passes away5.Confusable words.personal personnel / sometime sometimes some time sometime6.Euphemismd e h c g a b f7.Cloze.sponsored determination turned away assumed capacity skilled loan character hunting for sale send for save recent modest grow dream immigrant business engineering invest rich8.Translation.<1> It is reported that UN mediators have worked out a plan which they hope will beacceptable to both sides.<2> Doris walked in the forest cautiously, afraid of being attacked by giant snakes.<3> Earthquakes, typhoons and other natural disasters cannot be prevented, but action can betaken to protect life and property.<4> I bought a new issue of my favorite sports magazine and hurried home, anxious toamuse myself reading it.<5> Helen lacks confidence. I’ve never known anyone so unsure of herself.TranslationAfter graduating from college, Tony decided to start his own business. At the beginning, many a bank turned down his request for a loan. But he was not a bit discouraged, and continued to call on one banker after another seeking help. Impressed by his determination and optimism, one banker finally agreed to loan him the money. Now he has become a wealthy businessman. Talking about his amazing achievement, Tony puts great emphasis on the importance of creating, rather than waiting for opportunities.UNIT 5V ocabulary:1.monthly,2.acquaintances,3.classic,4.look in the eye5.manufacured6. options7. finance8. replacement9. survived 10. pick out 11. married 12. grabbed atRewrite:1.survived a car crash that killed both her parents.2.almost embarrassed to death when Sarah read my poem out to the whole class.3.of the Children’s Hospi tal will care for the seriously injured pupils./4.several phone calls making inquiries about the position of Chief Financial Officer.5.straighten out all your financial problems if you join our club.Complete:1.injury, died of hunger, people survived2.instantly, give up his, retire, replace him, executive3.his beloved, odd jobs, and all thatSuffixation:1. embarrassment2. survivors, 3 newly, 4. marketable5. monthly6. competition,7.conceivable8. respectableUsage:1. the poor, 2 the deceased\the dead 3. the disabled4. the French , 5 the accused 6. the young.7. the unemployed 8 the latter….the formerCloze:1. died of2. instantly, 3 classic, 4. ask around,5. surviving 6 . retire 7. executive, 8 replacement9 stock 10 look in the eye1 impressed2 diligence3 instead4 contrary5 professionally6 perform7 personal8 balance9 commitment 10 revealedTranslation:1.I’m not sure where you can find a good carpenter----you’d better ask around.2.Feeling a little embarrassed, he quickly cleared his throat and looked up at the painting on thewall.3.Michael was survived by three sons, two daughters, and his wife Elizabeth.4.As a financial expert, William advised us to invest our money in the stock market.5.We small r etailers can’t compete with supermarkets in pricing and sales.My dad is a hard-working executive of a manufacturing firm. He works six days a week. Every day he has to straighten out various kinds of problems so that he often stays up late/nights. However, he tries his best to balance/maintain a balance between work and family. On Sundays my dad usually stays at home and cares for us as much as he can. To my greatest joy, he cooks our favorite dishes and plays ball with us.Unit 6Translation:1) Before I went off to university, my grandfather gave me a few words of wisdom which impressed me deeply.2) Never tell my parents about my injuries and I’ll be very grateful to you (for it).3) At the meeting some of our colleagues put forward sensible suggestions about improving our working environment.4) The management has/ have agreed to grant the workers a 10% pay rise in response to union pressure.5) It was very thoughtful of the hostess to give the home a thorough cleaning before we arrived.6Not rich himself, Uncle Li never hesitates to help others. Previous to / Before his retirement, through Project Hope he located the addresses of two country kids who grew up in poor families but had a keen desire to study. From then on he sent them money regularly. Later the two made their way to college, and even got a chance to study overseas.UNIT 6Key to Exercises (Unit 6)V ocabulary:1.I:1) fertile 2) reflected 3) overseas 4) slim 5) split 6) sustained 7)glow8) thrust 9) keen 10)bud 11) previous 12) whichever2. 1) …of carpets and furniture in the bedroom disgusts me.2) …corresponding with Henry after the death of her mother.3)….is best located at an isolated place far from cities.4) …was so absorbed in the game on TV that I didn’t hear Martin come in.5)… players grip the ball.31) to broaden … make their way2) disgusts ….take a chance on3) the grand … and overseas ….reflectedII. Usage1. 1). frightened 2). afraid/frightened2. 1). alike/similar 2) similar3. 1) alive 2)living4. 1)sleeping 2) asleepIII. word family1. 1) disappointed2) disappointment 3) disappointing4) disappoint 5) disappointingly 6) disappointing2.1)attractive 2) attract 3) attraction4) attractively 5) unattractively 6) unattractiveComprehensive Exercises:III.Cloze(C)(1)—(10) identifying, gripped, margins, corresponding, overseas, more than a little,hesitated, grateful, made my way, going my way(D)(1)---(10) first, ring, Nor, another, threw, deliberately, reasoned, himself, restaurant, matter IV.Translation:1.Before I went off to university, my grandfather gave me a few words of wisdom whichimpressed me deeply.2.Never tell my parents about my injuries and I’ll be very grateful to you (for it).3.At the meeting some of our colleagues put forward sensible suggestions about improving ourworking environment.4.The management has agreed to grant the workers a 10% pay rise in response to unionpressure.5.It was very thoughtful of the hostess to give the house a thorough cleaning before we arrived.Not rich himself, Uncle Li never hesitates to help others. Previous to/ before his retirement,through Project Hope he located the addresses of two country kids who grew up in poor families but had a keen desire to study. From then on he sent them money regularly. Later the two made their way to college, and even got a chance to study overseas.Unit 7 Animal IntelligenceText A What Animals Really ThinkText OrganizationWorking on your ownDo the exercises and then compare your answers with a partner.1.The text is a piece of expository writing. As mentioned in Unit Three, the purpose ofexposition is to explain -- explain what a certain phenomenon means, how an operation works, etc. Now, think over what the author, Eugene Linden, wants to express here and write itdown.Eugene Linden wants to tell the reader that animals do have, at least, some limited intelligence, and the personal experiences of those who are in close contact with animals are more convincing evidence than that any experiments can provide.2.With subheadings the organization of the text is made very clear: the first two paragraphsserve as an introduction; it is followed by supporting facts grouped under three subheadings;the last paragraph is the conclusion. Now put down the main idea of each part under theirrespective subheadingsSubheadings Main IdeasLet's Make a Deal Some animals are intelligent enough to know how to bargain with people.Tale of a Whale Animals like whales can assess a situation and act accordingly. Primate Shell Game Animals sometimes can be tricky.VocabularyI1.Fill in the gaps with words or phrases chosen from the box. Change the form wherenecessary.1) go (very) far 2) has expanded 3) In the interest(s) of4) only to 5) encountered 6) has cooperated7) assessed 8) (had) switched 9) horizons10) gaze 11) disaster 12) wiped out2.Rewrite each sentence with the word or phrase in brackets, keeping the same meaning. Thefirst part has been written for you.1) a long /long-running controversy over whether the book should be published or not.2) felt relieved after her first meeting with Tom had gone smoothly.3) suddenly went wrong with my computer when I was in the middle of writing the essay.84) is obvious that our company is still maintaining its position as market leader insoftware.5) give in until they give her a pay rise.3. Complete the following sentences, using the words or phrases in brackets. Make additions orchanges where necessary.1) have undertaken original to explore2) evidence convinced underneath extending to3) to negotiate encounter to figure out exploreII. Confusable WordsFill in the gaps with at first or first or firstly according to the context:1. firstly2. first, first3. At first4. First/Firstly5. first6. First7. at first8. firstageFind out eight similar phrases from the text and tell how the attributive noun modifies another noun.Phrases In the phrase, the attributive noun indicates1. animalintelligence: whose2. zookeeper: where3. eyecontact: throughwhat4. moneysupply: of what5. killerwhale: whatkinde6. babywhale: how old7. family member: ofwhat8. sea turtle: whatkind/ whereComprehensive ExercisesI. Cloze1. 1. Text-related Complete the following passage with words chosen from the Words and Phrases to Drill box. Change the form where necessary.(1) emergency (2) evidence (3) original (4) sizing up(5) negotiates (6) reveal (7) make a deal (8)dominant (9)in their interest(s) (10) deceiving (11)controversy(12) judgment (13)explore2.Theme-related Read the passage carefully until you have got its main idea, and then select oneappropriate word for each gap from the box following the passage.(1) protect (2) However (3) type (4) situation (5) sights(6) together (7) rang (8) associate (9) without (10) environmentII. Translation1.Translate the sentences into English, using the words and phrases in brackets.1) A local business undertook the project but went bankrupt before it was completed.2)Let’s make a deal___ you wash my car, and I’ll let you use it tonight.3)We got to the village which we thought must have been wiped out in the severe earthquake,only to find it slightly damaged.4)My garden is dry and shady___ few plants thrive in that condition.5)Mystery s till surrounds the exact truth behind the film star’s death /exact circumstances of thefilm star’s death.2. Translate the passage into English, using the words and phrases given below.我小时候常去家乡的动物园参观。
打开英语字母的作文

打开英语字母的作文Title: The Essence of English Alphabets。
English alphabets, the building blocks of communication in the English language, are more than just symbols on a page. They carry with them a rich history, a plethora of sounds, and an intricate web of connections that shape the way we express ourselves. In this exploration, we delveinto the essence of English alphabets, uncovering their significance and unraveling the beauty they hold.A At the beginning of our journey lies the letter A, a symbol of beginnings and aspirations. It stands tall, representing ambition and achievement. From "apple" to "adventure," A initiates countless words, setting the stage for our linguistic exploration.B Bold and assertive, B follows closely behind, embodying strength and stability. It brings to mind words like "brave" and "bold," reminding us to embrace challengeswith resilience. B serves as a cornerstone, supporting the structure of our language.C Curving gracefully, C whispers of creativity and curiosity. It forms the foundation of words like "create" and "curious," encouraging us to explore the world around us. C is a reminder of the endless possibilities that lie within language.D D dances onto the scene with determination and diligence. It symbolizes dedication and drive, urging us to pursue our dreams with determination. From "dream" to "determination," D reminds us of the power of perseverance.E E emerges effortlessly, echoing with energy and enthusiasm. It epitomizes expression and excitement, infusing words with vitality. E is the heartbeat of our language, pulsating with passion and purpose.F Firm and focused, F strides forward with fortitude.It signifies focus and fearlessness, guiding us through challenges with confidence. F fuels our language with wordsof fortitude and faith.G Graceful yet grounded, G embodies growth and gratitude. It blooms with possibility, nurturing words of gratitude and guidance. G reminds us to be grateful for the gifts of language and to grow with each new word learned.H Holding steadfast, H symbolizes home and heart. It anchors us in our roots, connecting us to our heritage and history. H is a reminder of the importance of home and family, echoing in words of heartache and hope.I Illuminating our path, I shines with integrity and intelligence. It symbolizes individuality and insight, guiding us toward self-discovery. I invites introspection and inquiry, leading us to words of inspiration and innovation.J Joyful and jubilant, J dances with jubilation. It radiates joy and laughter, filling our language with jubilant expressions. J reminds us to find joy in the journey of language learning, celebrating each new wordmastered.K Kind and compassionate, K extends a hand of kindness. It embodies empathy and understanding, fosteringconnections between people. K encourages acts of kindness and words of compassion, bridging divides and building communities.L Leading with love, L embodies loyalty and laughter.It represents love and laughter, enriching our languagewith lightheartedness. L reminds us to embrace love in all its forms, weaving it into the fabric of our words.M Majestic and mystical, M commands attention with its magnitude. It symbolizes mystery and magic, sparking our imagination. M invites us to explore the depths of language, uncovering hidden meanings and metaphorical marvels.N Navigating through nuances, N delves into the intricacies of language. It represents nuance and subtlety, enriching our expressions with depth. N reminds us to pay attention to the finer details of language, embracing itsnuances with precision.O Open and optimistic, O radiates with optimism. It symbolizes openness and opportunity, inviting us to embrace new experiences. O reminds us of the endless possibilities that lie within language, encouraging us to explore with open minds and hearts.P Persevering with passion, P embodies perseverance and persistence. It symbolizes strength and determination, propelling us forward. P encourages us to push past obstacles and pursue our goals with passion.Q Quiet yet quintessential, Q adds a touch ofquirkiness to our language. It symbolizes uniqueness and individuality, standing out amidst the crowd. Q reminds usto embrace our quirks and quirks of language, celebrating the diversity of expression.R Resilient and resourceful, R rises to every challenge. It embodies resilience and adaptability, weathering storms with strength. R teaches us to embrace change and overcomeobstacles, leading us to words of resilience and resolve.S Spirited and spontaneous, S dances with spontaneity. It symbolizes spontaneity and adventure, infusing our language with excitement. S reminds us to embrace spontaneity and seek adventure in our linguistic journey.T Tenacious and timeless, T stands tall with tenacity. It embodies tenacity and tradition, grounding us in our roots. T connects us to the past while guiding us toward the future, weaving a tapestry of timeless tales and traditions.U Uniting with understanding, U fosters unity and understanding. It symbolizes harmony and empathy, bridging divides between people. U encourages us to seek common ground and build connections through language.V Vibrant and vivacious, V bursts with vitality. It symbolizes vibrancy and vigor, infusing our language with energy. V reminds us to approach language learning with enthusiasm and zest, embracing the vibrancy of words.W Wise and worldly, W whispers of wisdom and wonder. It embodies wisdom and wonder, inspiring us to explore the world. W invites us to wander through the words of language, uncovering wisdom along the way.X X marks the spot of exploration and excitement. It symbolizes the unknown and the extraordinary, leading us on adventures through language. X reminds us to embrace the unexpected and explore beyond the familiar.Y Yearning for connection, Y reaches out with yearning. It symbolizes yearning and yearning, bridging divides between people. Y reminds us of the importance ofconnection and community, weaving a web of words that unite us.Z Zealous and zestful, Z exudes zeal and zest. It symbolizes enthusiasm and energy, infusing our languagewith zeal. Z reminds us to approach language learning with zeal and zest, embracing each new word with excitement.In conclusion, English alphabets are not mere symbols but vessels of meaning and expression. From A to Z, they guide us through a journey of language and learning, enriching our lives with every word spoken and written. Let us continue to explore the beauty of English alphabets and unlock the endless possibilities they hold.。
高效液相色谱-荧光检测器法检测单克隆抗体注射液中吐温80的含量

Vol.7 No.1Feb. 2021生物化工Biological Chemical Engineering第 7 卷 第 1 期2021 年 2 月高效液相色谱-荧光检测器法检测单克隆抗体注射液中吐温80的含量张博慧,贾戴辉,许俊彦*(宝船生物医药科技(上海)有限公司药物分析部门,上海 201203)摘 要:目的:采用高效液相色谱-荧光检测器法(HPLC-FLD)测定单克隆抗体注射液中吐温80的含量,并进行方法学验证。
方法:按设定的色谱条件对检测单克隆抗体注射液中吐温80含量的HPLC-FLD 法进行方法学验证,包括专属性、精密度、准确度、线性和范围、耐用性,并采用该方法对不同单克隆抗体注射液进行检测。
结果:经验证,该方法具有专属性;重复性验证试验中,保留时间和含量的RSD 值分别为0.5%和0.4%;中间精密度验证试验中,保留时间和含量的RSD 值分别为0.4%和2.2%;准确度验证试验中,回收率分别为105%、98%和108%;线性相关系数为0.999 1,检测范围为0.05~0.80 mg/mL;不同批次反应线圈对检测结果无影响,不同品种单克隆抗体注射液吐温80含量检测结果偏差较小。
结论:该方法具有专属性,线性关系良好,精密度和准确度较好,测定结果稳定可靠,适用于单克隆抗体注射液中吐温80含量的检测。
关键词:高效液相色谱-荧光检测器;吐温80;单克隆抗体注射液中图分类号:R927.2 文献标识码:ADetermination of Tween80 Content in Monoclonal Antibody Injection by HPLC-FLDZHANG Bohui, JIA Daihui, XU Junyan *(Drug Analysis Department, Dragonboat Biopharmaceutical, Co., Ltd, Shanghai 201203)Abstract: Objective: To establish a method for the determination of Tween 80 in monoclonal antibody injection byHigh-performance liquid chromatography fluorescence detector. Methods: Under designed condition, the method was verified for specificity, precision, accuracy, linearity, range and durability. The method was also used to determination of Tween 80 content of different monoclonal antibody injections. Results: The HPLC-FLD method showed good specificity. In reproducibility test, the RSD of retention time and content were 0.5% and 0.4% respectively. In intermediate-precision test, the RSD of retention time and content were 0.4% and 2.2% respectively. The recovery rates were 105%, 98% and 108% respectively. The correlation Coefficient was 0.999 1 and the range was from 0.05 to 0.8 mg/mL. The different batches of reaction coils had no effect on the detection results. The Tween 80 contents in different mAb injections showed little deviation. Conclusion: The HPLC-FLD method showed good specificity, precision, accuracy and linearity, and the test result was stable and reliable, which was suitable for determination of Tween 80 content of different monoclonal antibody injections.Keywords: High-performance Liquid Chromatography-Fluorescence Detector; Tween 80; monoclonal antibody injection吐温80又名聚山梨酯80,其化学名为聚氧乙烯20山梨醇酐单油酸酯,作为助溶剂、乳化剂和稳定剂,常用于治疗性单克隆抗体注射液制剂中[1]。
高效液相色谱法测定保健食品纳豆红曲茶多酚软胶囊中洛伐他汀的方法

高效液相色谱法测定保健食品纳豆红曲茶多酚软胶囊中洛伐他汀的方法季加才,孟凡荣(山东润达检测技术有限公司,山东潍坊 261000)摘 要:目的:本文建立高效液相色谱法测定保健食品中(以纳豆红曲茶多酚软胶囊为例)洛伐他汀的方法。
方法:样品经乙腈提取后,用液相色谱C18柱分离,二元流动相洗脱,238 nm波长下紫外检测器检测,测定精密度、准确度。
结果:洛伐他汀在10~200 μg·mL-1线性关系良好,相关系数>0.999 9,相对标准偏差为0.62%。
当加标浓度为0.5 mg时,回收率为98.8%;当加标浓度为1.0 mg时,回收率为102.7%;当加标浓度为1.5 mg时,回收率为99.7%。
结论:本方法检测灵敏度高、操作简单、定性定量准确、针对性强,为纳豆红曲茶多酚软胶囊质量控制和深度开发提供了科学依据。
关键词:高效液相色谱法;洛伐他汀;纳豆红曲茶多酚软胶囊Determination of Lovastatin in Health Food Natto Monascus Tea Polyphenol Soft Capsules by High Performance LiquidChromatographyJI Jiacai, MENG Fanrong(Shandong Runda Testing Technology Co., Ltd., Weifang 261000, China) Abstract: Objective: To establish a method for the determination of lovastatin in health food by high performance liquid chromatography. Method: After being extracted with acetonitrile, the sample was separated using a liquid chromatography C18 column, eluted with a binary mobile phase, and detected with a UV detector at a wavelength of 238 nm for precision and accuracy. Result: The linear range of lovastatin was 10~200 μg·mL-1, the correlation coefficient was more than 0.999 9, and the relative standard deviation was 0.62%. When the concentration was 0.5 mg, the recovery rate was 98.8%. When the concentration was 1.0 mg, the recovery rate was 102.7%. When the concentration was 1.5 mg, the recovery rate was 99.7%. Conclusion : This method has high sensitivity, simple operation, accurate qualitative and quantitative, and strong pertinence. It provides a scientific basis for the quality control and in-depth development of natto monascus tea polyphenol soft capsule.Keywords: high performance liquid chromatography; lovastatin; natto monascus tea polyphenol soft capsules洛伐他汀由红曲霉在其生长后期产生,能有效降低血浆胆固醇[1]。
稳定性英文版

HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationFLUOXETINE HClC17H18F3NO•HClM.W. = 345.79CAS — 59333-67-4STABILITY INDICATINGA S S A Y V A L I D A T I O NMethod is suitable for:ýIn-process controlþProduct ReleaseþStability indicating analysis (Suitability - US/EU Product) CAUTIONFLUOXETINE HYDROCHLORIDE IS A HAZARDOUS CHEMICAL AND SHOULD BE HANDLED ONLY UNDER CONDITIONS SUITABLE FOR HAZARDOUS WORK.IT IS HIGHLY PRESSURE SENSITIVE AND ADEQUATE PRECAUTIONS SHOULD BE TAKEN TO AVOID ANY MECHANICAL FORCE (SUCH AS GRINDING, CRUSHING, ETC.) ON THE POWDER.ED. N0: 04Effective Date:APPROVED::HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationTABLE OF CONTENTS INTRODUCTION........................................................................................................................ PRECISION............................................................................................................................... System Repeatability ................................................................................................................ Method Repeatability................................................................................................................. Intermediate Precision .............................................................................................................. LINEARITY................................................................................................................................ RANGE...................................................................................................................................... ACCURACY............................................................................................................................... Accuracy of Standard Injections................................................................................................ Accuracy of the Drug Product.................................................................................................... VALIDATION OF FLUOXETINE HCl AT LOW CONCENTRATION........................................... Linearity at Low Concentrations................................................................................................. Accuracy of Fluoxetine HCl at Low Concentration..................................................................... System Repeatability................................................................................................................. Quantitation Limit....................................................................................................................... Detection Limit........................................................................................................................... VALIDATION FOR META-FLUOXETINE HCl (POSSIBLE IMPURITIES).................................. Meta-Fluoxetine HCl linearity at 0.05% - 1.0%........................................................................... Detection Limit for Fluoxetine HCl.............................................................................................. Quantitation Limit for Meta Fluoxetine HCl................................................................................ Accuracy for Meta-Fluoxetine HCl ............................................................................................ Method Repeatability for Meta-Fluoxetine HCl........................................................................... Intermediate Precision for Meta-Fluoxetine HCl......................................................................... SPECIFICITY - STABILITY INDICATING EVALUATION OF THE METHOD............................. FORCED DEGRADATION OF FINISHED PRODUCT AND STANDARD..................................1. Unstressed analysis...............................................................................................................2. Acid Hydrolysis stressed analysis..........................................................................................3. Base hydrolysis stressed analysis.........................................................................................4. Oxidation stressed analysis...................................................................................................5. Sunlight stressed analysis.....................................................................................................6. Heat of solution stressed analysis.........................................................................................7. Heat of powder stressed analysis.......................................................................................... System Suitability stressed analysis.......................................................................................... Placebo...................................................................................................................................... STABILITY OF STANDARD AND SAMPLE SOLUTIONS......................................................... Standard Solution...................................................................................................................... Sample Solutions....................................................................................................................... ROBUSTNESS.......................................................................................................................... Extraction................................................................................................................................... Factorial Design......................................................................................................................... CONCLUSION...........................................................................................................................ED. N0: 04Effective Date:APPROVED::HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationBACKGROUNDTherapeutically, Fluoxetine hydrochloride is a classified as a selective serotonin-reuptake inhibitor. Effectively used for the treatment of various depressions. Fluoxetine hydrochloride has been shown to have comparable efficacy to tricyclic antidepressants but with fewer anticholinergic side effects. The patent expiry becomes effective in 2001 (US). INTRODUCTIONFluoxetine capsules were prepared in two dosage strengths: 10mg and 20mg dosage strengths with the same capsule weight. The formulas are essentially similar and geometrically equivalent with the same ingredients and proportions. Minor changes in non-active proportions account for the change in active ingredient amounts from the 10 and 20 mg strength.The following validation, for the method SI-IAG-206-02 , includes assay and determination of Meta-Fluoxetine by HPLC, is based on the analytical method validation SI-IAG-209-06. Currently the method is the in-house method performed for Stability Studies. The Validation was performed on the 20mg dosage samples, IAG-21-001 and IAG-21-002.In the forced degradation studies, the two placebo samples were also used. PRECISIONSYSTEM REPEATABILITYFive replicate injections of the standard solution at the concentration of 0.4242mg/mL as described in method SI-IAG-206-02 were made and the relative standard deviation (RSD) of the peak areas was calculated.SAMPLE PEAK AREA#15390#25406#35405#45405#55406Average5402.7SD 6.1% RSD0.1ED. N0: 04Effective Date:APPROVED::HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationED. N0: 04Effective Date:APPROVED::PRECISION - Method RepeatabilityThe full HPLC method as described in SI-IAG-206-02 was carried-out on the finished product IAG-21-001 for the 20mg dosage form. The method repeated six times and the relative standard deviation (RSD) was calculated.SAMPLENumber%ASSAYof labeled amountI 96.9II 97.8III 98.2IV 97.4V 97.7VI 98.5(%) Average97.7SD 0.6(%) RSD0.6PRECISION - Intermediate PrecisionThe full method as described in SI-IAG-206-02 was carried-out on the finished product IAG-21-001 for the 20mg dosage form. The method was repeated six times by a second analyst on a different day using a different HPLC instrument. The average assay and the relative standard deviation (RSD) were calculated.SAMPLENumber% ASSAYof labeled amountI 98.3II 96.3III 94.6IV 96.3V 97.8VI 93.3Average (%)96.1SD 2.0RSD (%)2.1The difference between the average results of method repeatability and the intermediate precision is 1.7%.HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationLINEARITYStandard solutions were prepared at 50% to 200% of the nominal concentration required by the assay procedure. Linear regression analysis demonstrated acceptability of the method for quantitative analysis over the concentration range required. Y-Intercept was found to be insignificant.RANGEDifferent concentrations of the sample (IAG-21-001) for the 20mg dosage form were prepared, covering between 50% - 200% of the nominal weight of the sample.Conc. (%)Conc. (mg/mL)Peak Area% Assayof labeled amount500.20116235096.7700.27935334099.21000.39734463296.61500.64480757797.52000.79448939497.9(%) Average97.6SD 1.0(%) RSD 1.0ED. N0: 04Effective Date:APPROVED::HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationED. N0: 04Effective Date:APPROVED::RANGE (cont.)The results demonstrate linearity as well over the specified range.Correlation coefficient (RSQ)0.99981 Slope11808.3Y -Interceptresponse at 100%* 100 (%) 0.3%ACCURACYACCURACY OF STANDARD INJECTIONSFive (5) replicate injections of the working standard solution at concentration of 0.4242mg/mL, as described in method SI-IAG-206-02 were made.INJECTIONNO.PEAK AREA%ACCURACYI 539299.7II 540599.9III 540499.9IV 5406100.0V 5407100.0Average 5402.899.9%SD 6.10.1RSD, (%)0.10.1The percent deviation from the true value wasdetermined from the linear regression lineHPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationED. N0: 04Effective Date:APPROVED::ACCURACY OF THE DRUG PRODUCTAdmixtures of non-actives (placebo, batch IAG-21-001 ) with Fluoxetine HCl were prepared at the same proportion as in a capsule (70%-180% of the nominal concentration).Three preparations were made for each concentration and the recovery was calculated.Conc.(%)Placebo Wt.(mg)Fluoxetine HCl Wt.(mg)Peak Area%Accuracy Average (%)70%7079.477.843465102.27079.687.873427100.77079.618.013465100.0101.0100%10079.6211.25476397.910080.8011.42491799.610079.6011.42485498.398.6130%13079.7214.90640599.413080.3114.75632899.213081.3314.766402100.399.618079.9920.10863699.318079.3820.45879499.418080.0820.32874899.599.4Placebo, Batch Lot IAG-21-001HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationED. N0: 04Effective Date:APPROVED::VALIDATION OF FLUOXETINE HClAT LOW CONCENTRATIONLINEARITY AT LOW CONCENTRATIONSStandard solution of Fluoxetine were prepared at approximately 0.02%-1.0% of the working concentration required by the method SI-IAG-206-02. Linear regression analysis demonstrated acceptability of the method for quantitative analysis over this range.ACCURACY OF FLUOXETINE HCl AT LOW CONCENTRATIONThe peak areas of the standard solution at the working concentration were measured and the percent deviation from the true value, as determined from the linear regression was calculated.SAMPLECONC.µg/100mLAREA FOUND%ACCURACYI 470.56258499.7II 470.56359098.1III 470.561585101.3IV 470.561940100.7V 470.56252599.8VI 470.56271599.5(%) AverageSlope = 132.7395299.9SD Y-Intercept = -65.872371.1(%) RSD1.1HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationSystem RepeatabilitySix replicate injections of standard solution at 0.02% and 0.05% of working concentration as described in method SI-IAG-206-02 were made and the relative standard deviation was calculated.SAMPLE FLUOXETINE HCl AREA0.02%0.05%I10173623II11503731III10103475IV10623390V10393315VI10953235Average10623462RSD, (%) 5.0 5.4Quantitation Limit - QLThe quantitation limit ( QL) was established by determining the minimum level at which the analyte was quantified. The quantitation limit for Fluoxetine HCl is 0.02% of the working standard concentration with resulting RSD (for six injections) of 5.0%. Detection Limit - DLThe detection limit (DL) was established by determining the minimum level at which the analyte was reliably detected. The detection limit of Fluoxetine HCl is about 0.01% of the working standard concentration.ED. N0: 04Effective Date:APPROVED::HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationED. N0: 04Effective Date:APPROVED::VALIDATION FOR META-FLUOXETINE HCl(EVALUATING POSSIBLE IMPURITIES)Meta-Fluoxetine HCl linearity at 0.05% - 1.0%Relative Response Factor (F)Relative response factor for Meta-Fluoxetine HCl was determined as slope of Fluoxetine HCl divided by the slope of Meta-Fluoxetine HCl from the linearity graphs (analysed at the same time).F =132.7395274.859534= 1.8Detection Limit (DL) for Fluoxetine HClThe detection limit (DL) was established by determining the minimum level at which the analyte was reliably detected.Detection limit for Meta Fluoxetine HCl is about 0.02%.Quantitation Limit (QL) for Meta-Fluoxetine HClThe QL is determined by the analysis of samples with known concentration of Meta-Fluoxetine HCl and by establishing the minimum level at which the Meta-Fluoxetine HCl can be quantified with acceptable accuracy and precision.Six individual preparations of standard and placebo spiked with Meta-Fluoxetine HCl solution to give solution with 0.05% of Meta Fluoxetine HCl, were injected into the HPLC and the recovery was calculated.HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationED. N0: 04Effective Date:APPROVED::META-FLUOXETINE HCl[RECOVERY IN SPIKED SAMPLES].Approx.Conc.(%)Known Conc.(µg/100ml)Area in SpikedSampleFound Conc.(µg/100mL)Recovery (%)0.0521.783326125.735118.10.0521.783326825.821118.50.0521.783292021.55799.00.0521.783324125.490117.00.0521.783287220.96996.30.0521.783328526.030119.5(%) AVERAGE111.4SD The recovery result of 6 samples is between 80%-120%.10.7(%) RSDQL for Meta Fluoxetine HCl is 0.05%.9.6Accuracy for Meta Fluoxetine HClDetermination of Accuracy for Meta-Fluoxetine HCl impurity was assessed using triplicate samples (of the drug product) spiked with known quantities of Meta Fluoxetine HCl impurity at three concentrations levels (namely 80%, 100% and 120% of the specified limit - 0.05%).The results are within specifications:For 0.4% and 0.5% recovery of 85% -115%For 0.6% recovery of 90%-110%HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationED. N0: 04Effective Date:APPROVED::META-FLUOXETINE HCl[RECOVERY IN SPIKED SAMPLES]Approx.Conc.(%)Known Conc.(µg/100mL)Area in spikedSample Found Conc.(µg/100mL)Recovery (%)[0.4%]0.4174.2614283182.66104.820.4174.2614606187.11107.370.4174.2614351183.59105.36[0.5%]0.5217.8317344224.85103.220.5217.8316713216.1599.230.5217.8317341224.81103.20[0.6%]0.6261.3918367238.9591.420.6261.3920606269.81103.220.6261.3920237264.73101.28RECOVERY DATA DETERMINED IN SPIKED SAMPLESHPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationED. N0: 04Effective Date:APPROVED::REPEATABILITYMethod Repeatability - Meta Fluoxetine HClThe full method (as described in SI-IAG-206-02) was carried out on the finished drug product representing lot number IAG-21-001-(1). The HPLC method repeated serially, six times and the relative standard deviation (RSD) was calculated.IAG-21-001 20mg CAPSULES - FLUOXETINESample% Meta Fluoxetine % Meta-Fluoxetine 1 in Spiked Solution10.0260.09520.0270.08630.0320.07740.0300.07450.0240.09060.0280.063AVERAGE (%)0.0280.081SD 0.0030.012RSD, (%)10.314.51NOTE :All results are less than QL (0.05%) therefore spiked samples with 0.05% Meta Fluoxetine HCl were injected.HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationED. N0: 04Effective Date:APPROVED::Intermediate Precision - Meta-Fluoxetine HClThe full method as described in SI-IAG-206-02 was applied on the finished product IAG-21-001-(1) .It was repeated six times, with a different analyst on a different day using a different HPLC instrument.The difference between the average results obtained by the method repeatability and the intermediate precision was less than 30.0%, (11.4% for Meta-Fluoxetine HCl as is and 28.5% for spiked solution).IAG-21-001 20mg - CAPSULES FLUOXETINESample N o:Percentage Meta-fluoxetine% Meta-fluoxetine 1 in spiked solution10.0260.06920.0270.05730.0120.06140.0210.05850.0360.05560.0270.079(%) AVERAGE0.0250.063SD 0.0080.009(%) RSD31.514.51NOTE:All results obtained were well below the QL (0.05%) thus spiked samples slightly greater than 0.05% Meta-Fluoxetine HCl were injected. The RSD at the QL of the spiked solution was 14.5%HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationSPECIFICITY - STABILITY INDICATING EVALUATIONDemonstration of the Stability Indicating parameters of the HPLC assay method [SI-IAG-206-02] for Fluoxetine 10 & 20mg capsules, a suitable photo-diode array detector was incorporated utilizing a commercial chromatography software managing system2, and applied to analyze a range of stressed samples of the finished drug product.GLOSSARY of PEAK PURITY RESULT NOTATION (as reported2):Purity Angle-is a measure of spectral non-homogeneity across a peak, i.e. the weighed average of all spectral contrast angles calculated by comparing all spectra in the integrated peak against the peak apex spectrum.Purity Threshold-is the sum of noise angle3 and solvent angle4. It is the limit of detection of shape differences between two spectra.Match Angle-is a comparison of the spectrum at the peak apex against a library spectrum.Match Threshold-is the sum of the match noise angle3 and match solvent angle4.3Noise Angle-is a measure of spectral non-homogeneity caused by system noise.4Solvent Angle-is a measure of spectral non-homogeneity caused by solvent composition.OVERVIEWT he assay of the main peak in each stressed solution is calculated according to the assay method SI-IAG-206-02, against the Standard Solution, injected on the same day.I f the Purity Angle is smaller than the Purity Threshold and the Match Angle is smaller than the Match Threshold, no significant differences between spectra can be detected. As a result no spectroscopic evidence for co-elution is evident and the peak is considered to be pure.T he stressed condition study indicated that the Fluoxetine peak is free from any appreciable degradation interference under the stressed conditions tested. Observed degradation products peaks were well separated from the main peak.1® PDA-996 Waters™ ; 2[Millennium 2010]ED. N0: 04Effective Date:APPROVED::HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationFORCED DEGRADATION OF FINISHED PRODUCT & STANDARD 1.UNSTRESSED SAMPLE1.1.Sample IAG-21-001 (2) (20mg/capsule) was prepared as stated in SI-IAG-206-02 and injected into the HPLC system. The calculated assay is 98.5%.SAMPLE - UNSTRESSEDFluoxetine:Purity Angle:0.075Match Angle:0.407Purity Threshold:0.142Match Threshold:0.4251.2.Standard solution was prepared as stated in method SI-IAG-206-02 and injected into the HPLC system. The calculated assay is 100.0%.Fluoxetine:Purity Angle:0.078Match Angle:0.379Purity Threshold:0.146Match Threshold:0.4272.ACID HYDROLYSIS2.1.Sample solution of IAG-21-001 (2) (20mg/capsule) was prepared as in method SI-IAG-206-02 : An amount equivalent to 20mg Fluoxetine was weighed into a 50mL volumetric flask. 20mL Diluent was added and the solution sonicated for 10 minutes. 1mL of conc. HCl was added to this solution The solution was allowed to stand for 18 hours, then adjusted to about pH = 5.5 with NaOH 10N, made up to volume with Diluent and injected into the HPLC system after filtration.Fluoxetine peak intensity did NOT decrease. Assay result obtained - 98.8%.SAMPLE- ACID HYDROLYSISFluoxetine peak:Purity Angle:0.055Match Angle:0.143Purity Threshold:0.096Match Threshold:0.3712.2.Standard solution was prepared as in method SI-IAG-206-02 : about 22mg Fluoxetine HCl were weighed into a 50mL volumetric flask. 20mL Diluent were added. 2mL of conc. HCl were added to this solution. The solution was allowed to stand for 18 hours, then adjusted to about pH = 5.5 with NaOH 10N, made up to volume with Diluent and injected into the HPLC system.Fluoxetine peak intensity did NOT decrease. Assay result obtained - 97.2%.ED. N0: 04Effective Date:APPROVED::HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationSTANDARD - ACID HYDROLYSISFluoxetine peak:Purity Angle:0.060Match Angle:0.060Purity Threshold:0.099Match Threshold:0.3713.BASE HYDROLYSIS3.1.Sample solution of IAG-21-001 (2) (20mg/capsule) was prepared as per method SI-IAG-206-02 : An amount equivalent to 20mg Fluoxetine was weight into a 50mL volumetric flask. 20mL Diluent was added and the solution sonicated for 10 minutes. 1mL of 5N NaOH was added to this solution. The solution was allowed to stand for 18 hours, then adjusted to about pH = 5.5 with 5N HCl, made up to volume with Diluent and injected into the HPLC system.Fluoxetine peak intensity did NOT decrease. Assay result obtained - 99.3%.SAMPLE - BASE HYDROLYSISFluoxetine peak:Purity Angle:0.063Match Angle:0.065Purity Threshold:0.099Match Threshold:0.3623.2.Standard stock solution was prepared as per method SI-IAG-206-02 : About 22mg Fluoxetine HCl was weighed into a 50mL volumetric flask. 20mL Diluent was added. 2mL of 5N NaOH was added to this solution. The solution was allowed to stand for 18 hours, then adjusted to about pH=5.5 with 5N HCl, made up to volume with Diluent and injected into the HPLC system.Fluoxetine peak intensity did NOT decrease - 99.5%.STANDARD - BASE HYDROLYSISFluoxetine peak:Purity Angle:0.081Match Angle:0.096Purity Threshold:0.103Match Threshold:0.3634.OXIDATION4.1.Sample solution of IAG-21-001 (2) (20mg/capsule) was prepared as per method SI-IAG-206-02. An equivalent to 20mg Fluoxetine was weighed into a 50mL volumetric flask. 20mL Diluent added and the solution sonicated for 10 minutes.1.0mL of 30% H2O2 was added to the solution and allowed to stand for 5 hours, then made up to volume with Diluent, filtered and injected into HPLC system.Fluoxetine peak intensity decreased to 95.2%.ED. N0: 04Effective Date:APPROVED::HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationSAMPLE - OXIDATIONFluoxetine peak:Purity Angle:0.090Match Angle:0.400Purity Threshold:0.154Match Threshold:0.4294.2.Standard solution was prepared as in method SI-IAG-206-02 : about 22mg Fluoxetine HCl were weighed into a 50mL volumetric flask and 25mL Diluent were added. 2mL of 30% H2O2 were added to this solution which was standing for 5 hours, made up to volume with Diluent and injected into the HPLC system.Fluoxetine peak intensity decreased to 95.8%.STANDARD - OXIDATIONFluoxetine peak:Purity Angle:0.083Match Angle:0.416Purity Threshold:0.153Match Threshold:0.4295.SUNLIGHT5.1.Sample solution of IAG-21-001 (2) (20mg/capsule) was prepared as in method SI-IAG-206-02 . The solution was exposed to 500w/hr. cell sunlight for 1hour. The BST was set to 35°C and the ACT was 45°C. The vials were placed in a horizontal position (4mm vials, National + Septum were used). A Dark control solution was tested. A 2%w/v quinine solution was used as the reference absorbance solution.Fluoxetine peak decreased to 91.2% and the dark control solution showed assay of 97.0%. The difference in the absorbance in the quinine solution is 0.4227AU.Additional peak was observed at RRT of 1.5 (2.7%).The total percent of Fluoxetine peak with the degradation peak is about 93.9%.SAMPLE - SUNLIGHTFluoxetine peak:Purity Angle:0.093Match Angle:0.583Purity Threshold:0.148Match Threshold:0.825 ED. N0: 04Effective Date:APPROVED::HPLC ASSAY with DETERMINATION OF META-FLUOXETINE HCl.ANALYTICAL METHOD VALIDATION10 and 20mg Fluoxetine Capsules HPLC DeterminationSUNLIGHT (Cont.)5.2.Working standard solution was prepared as in method SI-IAG-206-02 . The solution was exposed to 500w/hr. cell sunlight for 1.5 hour. The BST was set to 35°C and the ACT was 42°C. The vials were placed in a horizontal position (4mm vials, National + Septum were used). A Dark control solution was tested. A 2%w/v quinine solution was used as the reference absorbance solution.Fluoxetine peak was decreased to 95.2% and the dark control solution showed assay of 99.5%.The difference in the absorbance in the quinine solution is 0.4227AU.Additional peak were observed at RRT of 1.5 (2.3).The total percent of Fluoxetine peak with the degradation peak is about 97.5%. STANDARD - SUNLIGHTFluoxetine peak:Purity Angle:0.067Match Angle:0.389Purity Threshold:0.134Match Threshold:0.8196.HEAT OF SOLUTION6.1.Sample solution of IAG-21-001-(2) (20 mg/capsule) was prepared as in method SI-IAG-206-02 . Equivalent to 20mg Fluoxetine was weighed into a 50mL volumetric flask. 20mL Diluent was added and the solution was sonicated for 10 minutes and made up to volume with Diluent. 4mL solution was transferred into a suitable crucible, heated at 105°C in an oven for 2 hours. The sample was cooled to ambient temperature, filtered and injected into the HPLC system.Fluoxetine peak was decreased to 93.3%.SAMPLE - HEAT OF SOLUTION [105o C]Fluoxetine peak:Purity Angle:0.062Match Angle:0.460Purity Threshold:0.131Match Threshold:0.8186.2.Standard Working Solution (WS) was prepared under method SI-IAG-206-02 . 4mL of the working solution was transferred into a suitable crucible, placed in an oven at 105°C for 2 hours, cooled to ambient temperature and injected into the HPLC system.Fluoxetine peak intensity did not decrease - 100.5%.ED. N0: 04Effective Date:APPROVED::。
quantificationof...
Research ArticleQuantification of Barbatusin and3β-Hydroxy-3-deoxybarbatusin in PlectranthusSpecies by HPLC-DADMaria Goretti de Vasconcelos Silva,Leandro Bezerra Lima,Maria da Conceição Ferreira de Oliveira,Marcos Carlos de Mattos,and Jair MafezoliPrograma de P´o s-Graduac¸˜a o em Qu´ımica,Universidade Federal do Cear´a,Campus do Pici,60455-970Fortaleza,CE,BrazilCorrespondence should be addressed to Jair Mafezoli;*************Received 23 April 2017; Accepted 4 June 2017; Published 3 July 2017Academic Editor:Neil D.DanielsonCopyright©2017Maria Goretti de Vasconcelos Silva et al.This is an open access article distributed under the Creative CommonsAttribution License,which permits unrestricted use,distribution,and reproduction in any medium,provided the original work isproperly cited.The concentration of diterpenes barbatusin(1)and3β-hydroxy-3-deoxybarbatusin(2)in the extracts from leaves of Plectranthusgrandis,P.barbatus,P.ornatus,and P.amboinicus was evaluated by HPLC-DAD analysis on a Luna C-18column,using isocraticmixtures of water and acetonitrile as eluents.The regression equations were obtained with good linearity(r2>0.99)and limit of quantifications was higher than0.1μg/mL.The precision(lower than3.5%,within day)and accuracy(higher than81.7%andlower than107.6%)of the methods were adequate.Barbatusin(1)was detected in P.grandis(15.432±2.28mg/g)and P.barbatus(5.198±3.45mg/g)extracts,while compound2was detected in P.grandis(4.068±3.34mg/g),P.barbatus(0.654±5.86mg/g),P.amboinicus(0.160±7.25mg/g),and P.ornatus(0.763±5.10mg/g).The evaluated validation parameters were satisfactorily achieved,and the developed methodology represents a suitable tool for application in the quantification of barbatusin(1)and3β-hydroxy-3-deoxybarbatusin(2)in Plectranthus species.1.IntroductionThe Plectranthus genus(Labiatae)is represented by ca.300 species,which occur essentially in Africa,Asia,Australia, and some Pacific islands.Several species of this genus are cultivated for their edible tubes or as essential oil crops.In addition,some species are used for medicinal purposes such as treating vomiting,nausea,and ear infections;relieving toothache,headache,sores,and burns;or as antiseptic[1]. Species of Plectranthus show biosynthetic ability to produce bioactive diterpenes like the labdane diterpenoid forskolin, from P.forskohlii,that shows significant blood pressure lowering properties[2]and the abietane diterpenoids coleon U and horminone that show antimicrobial activity against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecalis[3].In Brazil,Plectranthus species are popularly known as“boldo”and widely used as medicinal plants.P.grandis is used in the treatment of gastric and hepatic disturbs,and the gastric hyposecretory activity of this plant was already proven[4].Several diterpenes present in this plant have shown gastroprotective properties[5–7]. These results validate the popular use of P.grandis in the treatment of digestive problems.The abietane diterpenes bar-batusin(1)and3β-hydroxy-deoxybarbatusin(2)(Figure1) were isolated from P.grandis and P.barbatus[4,8]and showed good gastric protection activity in rats by oral admin-istration(10mg/kg).The reduction of the gastric lesions was about76%for1and96%for2[8].2.Experimental2.1.General.Acetonitrile and methanol(HPLC grade)were purchased from Tedia5.Deionized water was obtained from a Millipore Milli-Q system.All other solvents and reagents were purchased from Synth5.Chromatography columns were developed on silica(φmm0,063–0,200)purchased fromHindawiInternational Journal of Analytical Chemistry Volume 2017, Article ID 2397131, 5 pages https:///10.1155/2017/2397131OOO OHOAcOAcOOHO OHOAcOAc12Figure1:Chemical structures of barbatusin(1)and3β-hydroxy-3-deoxybarbatusin(2).Vetec5.Analytical TLC was performed on precoated0.25mm thick plates of silica gel60F254from Macherey-Nagel5,and the spots were visualized under UV lamp(254nm)and by spraying with a solution of perchloric acid-vanillin in EtOH, followed by heating.2.2.Plant Material.Leaves of P.grandis(#28377),P.barbatus (#24408),P.ornatus(#31929),and P.amboinicus(#28601), grown under environmental conditions at the Horto de Plantas Medicinais Francisco Jos´e de Abreu Matos(official medicinal plant garden from Cear´a state,Brazil),were col-lected in January2013,and their voucher specimens are deposited in Prisco Bezerra Herbarium-UFC.2.3.LC System and Chromatographic Method.A Shimadzu UFLC chromatographic system(model LC-20A),with DAD detector(Diode Assay Detector)SPD-M20A,and LC solu-tions software(version1.25)were used for data processing. The analyses were conducted on a Phenomenex5Luna5u C18(2)100A(250×4.60mm,5μm)analytical column in combination with a Phenomenex guard column.The methodology was based on the analysis of diterpenes in plants by HPLC-DAD[9].Isocratic elution with70% acetonitrile in water was used for compound1(method1)and 45%acetonitrile in water for compound2(method2).Both methods were carried out at flow rate of0.8mL/min.Tem-perature of the column was40∘C,and detection wavelength was254nm.Analyses were carried out in triplicate.2.4.Sample Preparation and Validation2.4.1.Isolation and Identification of Compounds1and2. The dried leaves(3.5Kg)of P.grandis were extracted with ethanol(5×8L)and yielded295.0g of extract after solvent evaporation under reduced pressure.The crude extract was dissolved in3L of water/methanol(4:6v/v)and submitted to liquid-liquid extraction with dichloromethane(6×100mL) to yield60.0g of dichloromethane fraction.Successive chro-matographic treatments in column,using SiO2as stationary phase and dichloromethane as mobile phase,gave3.4g of 1and140.0mg of2.The structures of both diterpenes were confirmed by high-resolution mass spectra,1H-NMR (500MHz,CDCl3),13C-NMR(125MHz,CDCl3),and com-parison with literature data[10].2.4.2.Preparation of Samples.Leaves from four Plectranthus species(P.grandis,P.barbatus,P.ornatus,and P.amboinicus) were dried at40∘C,pulverized to powder,and stored in a desiccator.An accurately weighted amount of1.0g of each sample was extracted with100mL of ethanol in ultrasonic bath during1hour at25∘C.Extracts were filtered and the solvent was completely removed by vacuum distillation at 40∘C.Each plant extract was dissolved in methanol(HPLC grade)and transferred to a25mL volumetric flask for a final concentration0.5mg/mL to be analyzed by HPLC-DAD.2.4.3.Preparation of Standard Solutions.Barbatusin(1)and 3β-3-hydroxy-3-deoxybarbatusin(2)isolated from leaves of P.grandis were used as standards for the analytical curves and method validation.Each diterpene was separately dissolved in methanol(HPLC grade),and the final concentration was adjusted to1.0mg/mL.The purities of standard compounds1 and2were determined as≥99%by HPLC-DAD analyses.2.4.4.Linearity and Selectivity.Solutions of the standard compounds1and2were prepared in methanol at25,50,100, 250,and500μg/mL.Then,20μL aliquots of these solutions were injected into HPLC equipment,in triplicate.For each analyte,the average peak area values were plotted against the respective concentrations,expressed inμg/mL.Both the cor-relation coefficient(r)and general standard curve equation were obtained from linear least-square regression analysis (Graphpad Prism55.03software).The method selectivity was determined through the analyses of the standard compounds 1and2and extracts of the four Plectranthus species.In all extracts,the peaks corresponding to1and2were identified by comparison of their retention times with those from the standard compounds.1200000400000600000800000(m A U )12345678Time (min)Method 1(a)2100000200000300000400000500000600000(m A U )246810121416Time (min)Method 2(b)1050000100000150000200000250000(m A U )12345678−1Time (min)Method 1(c)2−1000000100000200000300000400000500000600000700000(m A U )0246810121416−2Time (min)Method 2(d)Figure 2:HPLC chromatograms (254nm)of standard compounds 1(a)and 2(b)and the ethanol extract of P .grandis (c and d).2.4.5.Limits of Detection and Quantification.The limits of detection (LODs,S/N ≥3)of the two diterpenes 1and 2were 0.015and 0.22μg/mL,and the limits of quantification (LOQ,S/N ≥10)were 0.1and 0.6μg/mL,respectively.2.4.6.Precision and Repeatability.The precision of the method was evaluated in two levels,intraday and interdays.Intraday precision was evaluated by nine determinations (triplicate)in three different concentrations.Interdays pre-cision was evaluated using the same three concentrations,during two consecutive days,and by changing operators.The analyses were performed separately for each standard compound.The relative standard deviations (RSD)were calculated for each determination and taken as a measure of precision and repeatability.2.4.7.Accuracy.The accuracy was determined by recovery tests,which is an estimate of the accuracy of the meth-ods.Extracts containing known amounts of 1(166.5,249.0,and 374.0μg/mL)and 2(37.8,47.8,and 62.8μg/mL),in quintuplicate,were analyzed,besides the extracts with no addition of standard compounds.The recoveries of both standard compounds were calculated from the corresponding calibration curve according to the following equation:%recovery =(amount foundamount added)×100.(1)Table 1:Analytical parameters of linearity and limits of detection and quantification obtained for 1and 2.Analyte12Regression equation y =21496x −20448y =14145x +239256r 20.99310.9966LOD (μg/mL)0.0150.22LOQ (μg/mL)0.10.63.Results and DiscussionTwo analytical curves were obtained,one for each standard compound 1(method 1)and compound 2(method 2).The linearity of the concentrations versus peak area plot for both methods was determined,and good correlation coefficients were achieved (r 2=0.9931and r 2=0.9966).Table 1shows the linear regression equation and values for the LOD and LOQ which indicates that the developed methods are very sensitive and adequate for the investigated samples.The chro-matograms of 1and 2and P .grandis extract are shown in Figure 2.The intraday precision was evaluated by triplicate injec-tion at low,medium,and high concentrations levels.Rela-tive standard deviations were calculated based on observedTable2:Precision and accuracy for1and2in Plectranthus samples. Precision AccuracyAnalyte Amountμg/mLIntradayRSD(%)InterdayRSD(%)Amount added(μg/mL)Amount found(μg/mL)Recovery(mean±RSD,%,n=5)185.0 3.42 5.70186.5152.381.7±1.74 170.0 2.10 3.31249.0259.1104.0±2.10 680.0 1.92 6.01374.0384.0102.7±3.39265.0 3.44 2.6837.840.3107.6±3.60 130.0 3.34 6.2147.850.4105.4±2.94 325.0 1.3610.9562.864.1102.1±2.73Table3:Concentration of diterpenes1and2in leaves of Plectranthus species.Species1(mean±RSD,mg/g,n=3)2(mean±RSD,mg/g,n=3)P.grandis15.432±2.28 4.068±3.34 P.barbatus 5.197±3.450.654±5.86 P.ornatus Not detected0.763±5.10 P.amboinicus Not detected0.160±7.25concentrations.Naturally,interdays precision shows relative standard deviation greater than intraday.The accuracy was performed as recommended,by collecting data from a minimum of nine determinations over a minimum of three concentration levels[11].Table2shows the precision of the methods for1and2,which were accurate with recovery rates ranging from81.7to104.0%for1and from102.1to107.6%for 2.The found recovery rates(Table2)were acceptable since the objective of this study is mainly estimating the amount ofditerpenes1and2.Table3shows the concentration(mg/g)of diterpenes1and2in leaves of the investigated Plectranthus species.Bothcompounds were detected in P.grandis and P.barbatus whileP.ornatus and P.amboinicus showed only the presence of2.The highest concentrations of1and2were found in the leavesof P.grandis.Except in this species,diterpene2was foundin low concentration in the leaves of the studied species.Noamount of1in P.ornatus and P.amboinicus was observed bythe employed methodology.The lack of clear-cut morphological criteria to discrimi-nate some species of Plectranthus has resulted in numeroustaxonomic problems for identification of the specimens[1].Therefore,this work may represent a new tool for discrimi-nating Plectranthus species,by using compounds1and2aschemomarkers.4.ConclusionsIn summary,the analytical methods were adequate forquantification of diterpenes1and2in the leaves of fourPlectranthus species.Barbatusin(1)was identified only in theextracts from P.grandis and P.barbatus,while compound2was present in all Plectranthus species.The highest amount of both compounds1and2was found in P.grandis.This is the first report on the identification of3β-hydroxy-3-deoxybarbatusin(2)in the extracts from P.amboinicus and P.ornatus.Conflicts of InterestThe authors declare that they have no conflicts of interest. AcknowledgmentsThe authors wish to thank Fundac¸˜a o Cearense de Apoio a Pesquisa(FUNCAP),Conselho Nacional do Desenvolvi-mento Cient´ıfico e Tecnol´o gico(CNPq),and Coordenac¸˜a o de Aperfeic¸oamento de Pessoal de N´ıvel Superior(CAPES)for financial support.References[1]C.W.Lukhoba,M.S.J.Simmonds,and A.J.Paton,“Plectran-thus:a review of ethnobotanical uses,”Journal of Ethnopharma-cology,vol.103,no.1,pp.1–24,2006.[2]H.Hagiwara,F.Takeuchi,T.Hoshi,T.Suzuki,T.Hashimoto,and Y.Asakawa,“First synthesis of1,9-dideoxyforskolin from ptychantin A,”Tetrahedron Letters,vol.44,no.11,pp.2305-2306, 2003.[3]C.Gaspar-Marques,P.Rijo,M.F.Sim˜o es,M.A.Duarte,and B.Rodriguez,“Abietanes from Plectranthus grandidentatus and P.hereroensis against methicillin-and vancomycin-resistant bac-teria,”Phytomedicine,vol.13,no.4,pp.267–271,2006.[4]L.A.Fischman,L.A.Skorupa,C.Souccar,and pa,“The water extract of Coleus barbatus Benth decreases gastric secretion in rats,”Memorias do Instituto Oswaldo Cruz,vol.86, p.141,1991.[5]G.Schmeda-Hirschmann,J.Rodriguez,and L.Astudillo,“Gas-troprotective activity of the diterpene solidagenone and its derivatives on experimentally induced gastric lesions in mice,”Journal of Ethnopharmacology,vol.81,no.1,pp.111–115,2002.[6]P.S.Melo,N.Dur´a n,C.A.Hiruma-Lima,A.R.M.Souza-Brito,and M.Haun,“Comparison of the gastroprotective effect of a diterpene lactone isolated from Croton cajucara with its synthetic derivatives,”Journal of Ethnopharmacology,vol.87,no.2-3,pp.169–174,2003.[7]J. A.Rodr´ıguez, C.Theoduloz,T.Y´a˜n ez,J.Becerra,andG.Schmeda-Hirschmann,“Gastroprotective and ulcer healingeffect of ferruginol in mice and rats:Assessment of its mecha-nism of action using in vitro models,”Life Sciences,vol.78,no.21,pp.2503–2509,2006.[8]P.D.A.Rodrigues,S.M.de Morais,C.M.de Souza et al.,“Gastroprotective effect of barbatusin and3-beta-hydroxy-3-deoxibarbatusin,quinonoid diterpenes isolated from Plectran-thus grandis,in ethanol-induced gastric lesions in mice,”Journal of Ethnopharmacology,vol.127,no.3,pp.725–730,2010. [9]J.Yin,Y.Wang,B.Tan et al.,“Matrix solid-phase disper-sion extraction for chromatographic analysis of labdane diter-penoids in coleus forskohlii,”Phytochemical Analysis,vol.24, no.2,pp.117–123,2013.[10]R.L.De Albuquerque,M.R.Kentopff,M.I.L.Machado et al.,“Abietane diterpenoids isolation from Plectranthus barbatus,”Quimica Nova,vol.30,p.1882,2007.[11]G.A.Shabir,“Validation of high-performance liquid chro-matography methods for pharmaceutical analysis:understand-ing the differences and similarities between validation require-ments of the US Food and Drug Administration,the US Pharmacopeia and the International Conference on Harmo-nization,”Journal of Chromatography A,vol.987,no.1-2,pp.57–66,2003.Inorganic ChemistryInternational Journal ofInternational Journal ofPhotoenergyCarbohydrate ChemistryInternational Journal of nal ofJournal ofChemistryAdvances inPhysical ChemistryA nalytical Methods in ChemistryJournal ofBioinorganic Chemistry and ApplicationsSpectroscopyInternational Journal ofMedicinal ChemistryInternational Journal ofC hromatography Research InternationalApplied ChemistryJournal ofTheoretical ChemistryJournal ofJournal ofSpectroscopyAnalytical ChemistryInternational Journal ofJournal ofQuantum ChemistryO rganic Chemistry InternationalElectrochemistryInternational Journal ofCatalystsJournal of。
生活饮用水中镉含量3种检测方法的比较
• 136 •江苏预防医学 2021 年 3 月第 32 卷第2 期Jiangsu J Prev M ed,M ar.,2021, Vol. 32,No. 2•专题论著•生活饮用水中镉含量3种检测方法的比较吴勇、张路、韦超峰、朱慧、曹蕾21•黄山市疾病预防控制中心,安徽黄山245000;2•皖南医学院摘要:目的探讨测定生活饮用水中镉(C d)的简便、快捷、实用方法。
方法以黄山市2019年城区住宅小区末梢水、黄山风景区水、井水为研究对象,以相关系数、检出限、加标回收率、精密度等指标,比较3种国标推荐的生活饮用水中镉的测定方法(火焰原子吸收分光光度法、石墨炉原子吸收分光光度法、电感耦合等离子体质谱法)优缺点。
结果火焰原子吸收分光光度法、石墨炉原子吸收分光光度法和电感耦合等离子体质谱法的线性关系均较好,方法的相关系数「分别为0.999 92、0.999 99、0.999 72,方法的检出限分别为 0.〇5 mg/L、0.5 p g/L、0.5 伴/L,回收率分别为 76.37%、97.06%、99.49%;方法的相对标准偏差(K S D)分别为1.46%、2.42%、2.08%。
结论3种方法各有优缺点,检验人员应熟悉各类仪器,不断学习新操作技能,适应检验检测要求。
关键词:生活饮用水;镉(C d);火焰原子吸收分光光度法;石墨炉原子吸收分光光度法;电感耦合等离子体质谱法中图分类号:R113 文献标识码:A文章编号:1006-9070(2021)02-0136-03Comparison of three methods for determination of cadmium in drinking waterW U Y ong' ,ZHA NG L u.W E I C hao-feng,ZH U H ui.C A O LeiHuatigshuti M unicipal Center fo r Disease Control and Prevention A nhui H uangshan 2A5000 ^Chi?ia Abstract: Objective To explore a sim ple,rapid and practical method for the determination of cadmium (C d) in drinking water. Methods Taking the peripheral w ater of H uangshan urban residential area. H uangshan Scenic Area and well w ater in2019 as the research objects, three kinds of national standard recommended determination methodvS of cadmium in drinking suchas flame atomic absorption spectrom etry,graphite furnace atomic absorption spectrom etry and inductively coupled plasma mass spectrom etry w ater were compared, the corresponding correlation coefficient, detection lim it. recovery rate and precision were calculated for evaluation of advantages and disadvantages. Results The linear relation of flame atomic absorption spectrophotom etry, graphite furnace atomic absorption spectrophotom etry and inductively coupled plasma mass spectrom etry were good.The correlation coefficients were 0. 999 92,0. 999 99 and 0. 999 72. The detection limits were 0. 05 m g/L,0. 5 }i g/L and 0. S jig/L, respectively.The recovery rate was 76. 37% ,97. 06% ,99. 49% , respectively; the relative standard deviations of the methodwere 1. 46%, 2. 42%, 2. 08%»respectively. Conclusion Every method has advantages and disadvantages. The researchers should be familiar with all kinds of instrum ents and learn new operation skills constantly to adapt to the experimental requirements.Key words:Drinking w ater; Cadm ium; Flame atomic absorption spectrom etry; Graphite furnace atomic absorption spectrom etry; Inductively coupled plasma mass spectrom etry生活饮用水安全是影响人体健康和国计民生的 重大问题[12],选择科学合理的评价方法,对于客观反 映其质量尤为重要[3]。
水质石油类和动植物油类新旧标准测定方法比对
水质石油类和动植物油类新旧标准测定方法比对赵汝丽【摘要】通过新(HJ 637-2012)旧(GB /T 16488-1996)标准方法测定环境标准样品和环境样品中的石油类的实验结果分析、比对,显示使用新旧标准方法,样品测定结果无显著性差异,准确度和精密度均满足实验室质量控制要求;且新标准方法操作步骤更为简化,萃取在相对密闭的体系中完成,使萃取更完全,即提高了样品分析的准确度还减少了有机试剂对操作人员的健康危害和对环境的污染。
%The determination of oil using both the old (GB /T16488 -1996)and the new (HJ637 -2012)stand-ard methods were analyzed and compared.The results showed that the test results had no significant difference by two standard methods.Both accuracy and precision could meet the requirements of quality control.Moreover,the new method had much simpler steps.The extraction was done in a closed system that fulfilled a complete extrac-tion.Therefore,the new methods not only increased the accuracy but also reduced the negative impacts of the or-ganic agents on people's health and environment.【期刊名称】《环境科学导刊》【年(卷),期】2015(000)0z1【总页数】5页(P82-86)【关键词】石油类;测定;新旧标准方法;比对【作者】赵汝丽【作者单位】大理州环境监测站,云南大理 671000【正文语种】中文【中图分类】X83环境水中的石油类污染主要来自工业废水和生活污水。
USP-化学药物质量控制分析方法验证技术指导原则
1225VALIDATION OF COMPENDIAL PROCEDURESTest procedures for assessment of the quality levels of pharmaceutical articles are subject to various requirements. According to Section 501 of the Federal Food, Drug, and Cosmetic Act, assays and specifications in monographs of the United States Pharmacopeia and the National Formulary constitute legal standards. The Current Good Manufacturing Practice regulations [21 CFR 211.194(a)] require that test methods, which are used for assessing compliance of pharmaceutical articles with established specifications, must meet proper standards of accuracy and reliability. Also, according to these regulations [21 CFR 211.194(a)(2)], users of analytical methods described in USP–NF are not required to validate the accuracy and reliability of these methods, but merely verify their suitability under actual conditions of use. Recognizing the legal status of USP and NF standards, it is essential, therefore, that proposals for adoption of new or revised compendial analytical procedures be supported by sufficient laboratory data to document their validity.The text of this information chapter harmonizes, to the extent possible, with the Tripartite International Conference on Harmonization (ICH) documents Validation of Analytical Procedures and the Methodology extension text, which are concerned with analytical procedures included as part of registration applications submitted within the EC, Japan, and the USA.SUBMISSIONS TO THE COMPENDIASubmissions to the compendia for new or revised analytical procedures should contain sufficient information to enable members of the USP Council of Experts and its Expert Committees to evaluate the relative merit of proposed procedures. In most cases, evaluations involve assessment of the clarity and completeness of the description of the analytical procedures, determination of the need for the procedures, and documentation that they have been appropriately validated. Information may vary depending upon the type ofmethod involved. However, in most cases a submission will consist of the following sections.Rationale— This section should identify the need for the procedure and describe the capability of the specific procedure proposed and why it is preferred over other types of determinations. For revised procedures, a comparison should be provided of limitations of the current compendial procedure and advantages offered by the proposed procedure.Proposed Analytical Procedure— This section should contain a complete description of the analytical procedure sufficiently detailed to enable persons “skilled in the art” to replicate it. The write-up should include all important operational parameters and specific instructions such as preparation of reagents, performance of system suitability tests, description of blanks used, precautions, and explicit formulas for calculation of test results.Data Elements— This section should provide thorough and complete documentation of the validation of the analytical procedure. It should include summaries of experimental data and calculations substantiating each of the applicable analytical performance characteristics. These characteristics are described in the following section.VALIDATIONValidation of an analytical procedure is the process by which it is established, by laboratory studies, that the performance characteristics of the procedure meet the requirements for the intended analytical applications. Typical analytical performance characteristics that should be considered in the validation of the types of procedures described in this document are listed in Table 1. Because opinions may differ with respect to terminology and use, each of the performance characteristics is defined in the next section of this chapter, along with a delineation of a typical method or methods by which it may be measured. The definitions refer to “test results.” The description of the analytical procedure should define what the test results for the procedure are. As notedin ISO 5725-1 and 3534-1, a test result is “the value of a characteristic obtained by carrying out a specified test method. The test method should specify that one or a number of individual measurements be made, and their average, or another appropriate function (such as the median or the standard deviation), be reported as the test result. It may also require standard corrections to be applied, such as correction of gas volumes to standard temperature and pressure. Thus, a test result can be a result calculated from several observed values. In the simple case, the test result is the observed value itself.” A test result also can be, but need not be, the final, reportable value that would be compared to the acceptance criteria of a specification. Validation of physical property methods may involve the assessment of chemometric models. However, the typical analytical characteristics used in method validation can be applied to the methods derived from the use of the chemometric models.The effects of processing conditions and potential for segregation of materials should be considered when obtaining a representative sample to be used for validation of procedures.Table 1. Typical Analytical CharacteristicsUsed in Method ValidationAccuracyPrecisionSpecificityDetection LimitQuantitation LimitLinearityRangeRobustnessIn the case of compendial procedures, revalidation may be necessary in the following cases: a submission to the USP of a revised analytical procedure; or the use of an established general procedure with a new product or raw material (see below in Data Elements Required for Validation).The ICH documents give guidance on the necessity for revalidation in the following circumstances: changes in the synthesis of the drug substance; changes in the composition of the drug product; and changes in the analytical procedure.Chapter 1225is intended to provide information that is appropriate to validate a wide range of compendial analytical procedures. The validation of compendial procedures may use some or all of the suggested typical analytical characteristics used in method validation as outlined in Table 1 and categorized by type of analytical method in Table 2. For some compendial procedures the fundamental principles of validation may extend beyond characteristics suggested in Chapter 1225. For these procedures the user is referred to the individual compendial chapter for those specific analytical validation characteristics and any specific validation requirements.Analytical Performance CharacteristicsaccuracyDefinition— The accuracy of an analytical procedure is the closeness of test results obtained by that procedure to the true value. The accuracy of an analytical procedure should be established across its range. [A note on terminology: The definition of accuracy in 1225and ICH Q2 corresponds to unbiasedness only. In the International Vocabulary of Metrology (VIM) and documents of the International Organization for Standardization (ISO), “accuracy” has a di fferent meaning. In ISO, accuracy combines the concepts of unbiasedness (termed “trueness”) and precision.]Determination— In the case of the assay of a drug substance, accuracy may be determined by application of the analytical procedure to an analyte of known purity (e.g., a Reference Standard) or by comparison of the results of the procedure with those of a second, well-characterized procedure, the accuracy of which has been stated or defined.In the case of the assay of a drug in a formulated product, accuracy may be determined by application of the analytical procedure to synthetic mixtures of the drug product components to which known amounts of analyte have been added within the range of the procedure. If it is not possible to obtain samples of all drug product components, it may be acceptable either to add known quantities of the analyte to the drug product (i.e., “to spike”) or to compare results with those of a second, well-characterized procedure, the accuracy of which has been stated or defined.In the case of quantitative analysis of impurities, accuracy should be assessed on samples (of drug substance or drug product) spiked with known amounts of impurities. Where it is not possible to obtain samples of certain impurities or degradation products, results should be compared with those obtained by an independent procedure. In the absence of other information, it may be necessary to calculate the amount of an impurity based on comparison of its response to that of the drug substance; the ratio of the responses of equal amounts of the impurity and the drug substance (relative response factor) should be used if known.Accuracy is calculated as the percentage of recovery by the assay of the known added amount of analyte in the sample, or as the difference between the mean and the accepted true value, together with confidence intervals.The ICH documents recommend that accuracy should be assessed using a minimum of nine determinations over a minimum of three concentration levels, covering the specified range (i.e., three concentrations and three replicates of each concentration).Assessment of accuracy can be accomplished in a variety of ways, including evaluating the recovery of the analyte (percent recovery) across the range of the assay, or evaluating the linearity of the relationship between estimated and actual concentrations. The statistically preferred criterion is that the confidence interval for the slope be contained in an interval around 1.0, or alternatively, that the slope be close to 1.0. In either case, the interval or the definition ofcloseness should be specified in the validation protocol. The acceptance criterion will depend on the assay and its variability and on the product. Setting an acceptance criterion based on the lack of statistical significance of the test of the null hypothesis that the slope is 1.0 is not an acceptable approach. Accuracy of physical property methods may be assessed through the analysis of standard reference materials, or alternatively, the suitability of the above approaches may be considered on a case-by-case basis.precisionDefinition— The precision of an analytical procedure is the degree of agreement among individual test results when the procedure is applied repeatedly to multiple samplings of a homogeneous sample. The precision of an analytical procedure is usually expressed as the standard deviation or relative standard deviation (coefficient of variation) of a series of measurements. Precision may be a measure of either the degree of reproducibility or of repeatability of the analytical procedure under normal operating conditions. In this context, reproducibility refers to the use of the analytical procedure in different laboratories, as in a collaborative study. Intermediate precision (also known as ruggedness) expresseswithin-laboratory variation, as on different days, or with different analysts or equipment within the same laboratory. Repeatability refers to the use of the analytical procedure within a laboratory over a short period of time using the same analyst with the same equipment.Determination— The precision of an analytical procedure is determined by assaying a sufficient number of aliquots of a homogeneous sample to be able to calculate statistically valid estimates of standard deviation or relative standard deviation (coefficient of variation). Assays in this context are independent analyses of samples that have been carried through the complete analytical procedure from sample preparation to final test result.The ICH documents recommend that repeatability should be assessed using a minimum of nine determinations covering the specified range for the procedure(i.e., three concentrations and three replicates of each concentration) or using a minimum of six determinations at 100% of the test concentration.specificityDefinition— The ICH documents define specificity as the ability to assess unequivocally the analyte in the presence of components that may be expected to be present, such as impurities, degradation products, and matrix components. Lack of specificity of an individual analytical procedure may be compensated by other supporting analytical procedures. [Note—Other reputable international authorities (IUPAC, AOAC-I) have preferred the term “selectivity,” reserving “specificity” for tho se procedures that are completely selective. ] For the tests discussed below, the above definition has the following implications:Identification Tests: ensure the identity of the analyte.Purity Tests: ensure that all the analytical procedures performed allow an accurate statement of the content of impurities of an analyte (e.g., related substances test, heavy metals limit, organic volatile impurities).Assays: provide an exact result, which allows an accurate statement on the content or potency of the analyte in a sample.Determination— In the case of qualitative analyses (identification tests), the ability to select between compounds of closely related structure that are likely to be present should be demonstrated. This should be confirmed by obtaining positive results (perhaps by comparison to a known reference material) from samples containing the analyte, coupled with negative results from samples that do not contain the analyte and by confirming that a positive response is not obtained from materials structurally similar to or closely related to the analyte.In the case of analytical procedures for impurities, specificity may be established by spiking the drug substance or product with appropriate levels of impurities and demonstrating that these impurities are determined with appropriate accuracy and precision.In the case of the assay, demonstration of specificity requires that it can be shown that the procedure is unaffected by the presence of impurities or excipients. In practice, this can be done by spiking the drug substance or product with appropriate levels of impurities or excipients and demonstrating that the assay result is unaffected by the presence of these extraneous materials.If impurity or degradation product standards are unavailable, specificity may be demonstrated by comparing the test results of samples containing impurities or degradation products to a second well-characterized procedure (e.g., a Pharmacopeial or other validated procedure). These comparisons should include samples stored under relevant stress conditions (e.g., light, heat, humidity, acid/base hydrolysis, and oxidation). In the case of the assay, the results should be compared; in the case of chromatographic impurity tests, the impurity profiles should be compared.The ICH documents state that when chromatographic procedures are used, representative chromatograms should be presented to demonstrate the degree of selectivity, and peaks should be appropriately labeled. Peak purity tests (e.g., using diode array or mass spectrometry) may be useful to show that the analyte chromatographic peak is not attributable to more than one component.For validation of specificity for qualitative and quantitative determinations by spectroscopic methods, chapters related to topics such as near-infrared spectrophotometry, raman spectroscopy, and X-ray powder diffraction should be consulted.detection limitDefinition— The detection limit is a characteristic of limit tests. It is the lowest amount of analyte in a sample that can be detected, but not necessarily quantitated, under the stated experimental conditions. Thus, limit tests merely substantiate that the amount of analyte is above or below a certain level. Thedetection limit is usually expressed as the concentration of analyte (e.g., percentage, parts per billion) in the sample.Determination— For noninstrumental procedures, the detection limit is generally determined by the analysis of samples with known concentrations of analyte and by establishing the minimum level at which the analyte can be reliably detected.For instrumental procedures, the same approach may be used as for noninstrumental procedures. In the case of procedures submitted for consideration as official compendial procedures, it is almost never necessary to determine the actual detection limit. Rather, the detection limit is shown to be sufficiently low by the analysis of samples with known concentrations of analyte above and below the required detection level. For example, if it is required to detect an impurity at the level of 0.1%, it should be demonstrated that the procedure will reliably detect the impurity at that level.In the case of instrumental analytical procedures that exhibit background noise, the ICH documents describe a common approach, which is to compare measured signals from samples with known low concentrations of analyte with those of blank samples. The minimum concentration at which the analyte can reliably be detected is established. Typically acceptable signal-to-noise ratios are 2:1 or 3:1. Other approaches depend on the determination of the slope of the calibration curve and the standard deviation of responses. Whatever method is used, the detection limit should be subsequently validated by the analysis of a suitable number of samples known to be near, or prepared at, the detection limit.quantitation limitDefinition— The quantitation limit is a characteristic of quantitative assays for low levels of compounds in sample matrices, such as impurities in bulk drug substances and degradation products in finished pharmaceuticals. It is the lowest amount of analyte in a sample that can be determined with acceptable precision and accuracy under the stated experimental conditions. Thequantitation limit is expressed as the concentration of analyte (e.g., percentage, parts per billion) in the sample.Determination— For noninstrumental procedures, the quantitation limit is generally determined by the analysis of samples with known concentrations of analyte and by establishing the minimum level at which the analyte can be determined with acceptable accuracy and precision.For instrumental procedures, the same approach may be used as for noninstrumental procedures. In the case of procedures submitted for consideration as official compendial procedures, it is almost never necessary to determine the actual quantitation limit. Rather, the quantitation limit is shown to be sufficiently low by the analysis of samples with known concentrations of analyte above and below the quantitation level. For example, if it is required that an analyte be assayed at the level of 0.1 mg per tablet, it should be demonstrated that the procedure will reliably quantitate the analyte at that level.In the case of instrumental analytical procedures that exhibit background noise, the ICH documents describe a common approach, which is to compare measured signals from samples with known low concentrations of analyte with those of blank samples. The minimum concentration at which the analyte can reliably be quantified is established. A typically acceptable signal-to-noise ratio is 10:1. Other approaches depend on the determination of the slope of the calibration curve and the standard deviation of responses. Whatever approach is used, the quantitation limit should be subsequently validated by the analysis of a suitable number of samples known to be near, or prepared at, the quantitation limit.linearity and rangeDefinition of Linearity— The linearity of an analytical procedure is its ability to elicit test results that are directly, or by a well-defined mathematical transformation, proportional to the concentration of analyte in samples within a given range. Thus, in this section, “linearity” refers to the linearity of therelationship of concentration and assay measurement. In some cases, to attain linearity, the concentration and/or the measurement may be transformed. (Note that the weighting factors used in the regression analysis may change when a transformation is applied.) Possible transformations may include log, square root, or reciprocal, although other transformations are acceptable. If linearity is not attainable, a nonlinear model may be used. The goal is to have a model, whether linear or nonlinear, that describes closely the concentration-response relationship.Definition of Range— The range of an analytical procedure is the interval between the upper and lower levels of analyte (including these levels) that have been demonstrated to be determined with a suitable level of precision, accuracy, and linearity using the procedure as written. The range is normally expressed in the same units as test results (e.g., percent, parts per million) obtained by the analytical procedure.Determination of Linearity and Range— Linearity should be established across the range of the analytical procedure. It should be established initially by visual examination of a plot of signals as a function of analyte concentration of content. If there appears to be a linear relationship, test results should be established by appropriate statistical methods (e.g., by calculation of a regression line by the method of least squares). Data from the regression line itself may be helpful to provide mathematical estimates of the degree of linearity. The correlation coefficient, y-intercept, slope of the regression line, and residual sum of squares should be submitted.The range of the procedure is validated by verifying that the analytical procedure provides acceptable precision, accuracy, and linearity when applied to samples containing analyte at the extremes of the range as well as within the range.ICH recommends that, for the establishment of linearity, a minimum of five concentrations normally be used. It is also recommended that the following minimum specified ranges should be considered:Assay of a Drug Substance (or a finished product): from 80% to 120% of the test concentration.Determination of an Impurity: from 50% to 120% of the acceptance criterion. For Content Uniformity: a minimum of 70% to 130% of the test concentration, unless a wider or more appropriate range based on the nature of the dosage form (e.g., metered-dose inhalers) is justified.For Dissolution Testing: ±20% over the specified range (e.g., if the acceptance criteria for a controlled-release product cover a region from 30%, after 1 hour, and up to 90%, after 24 hours, the validated range would be 10% to 110% of the label claim).The traditional definition of linearity, i.e., the establishment of a linear or mathematical relationship between sample concentration and response, is not applicable to particle size analysis. For particle size analysis, a concentration range is defined (instrument- and particle size-dependent) such that the measured particle size distribution is not affected by changes in concentration within the defined concentration range. Concentrations below the defined concentration range may introduce an error due to poor signal-to-noise ratio, and concentrations exceeding the defined concentration range may introduce an error due to multiple scattering.robustnessDefinition— The robustness of an analytical procedure is a measure of its capacity to remain unaffected by small but deliberate variations in procedural parameters listed in the procedure documentation and provides an indication of its suitability during normal usage. Robustness may be determined during development of the analytical procedure.system suitabilityIf measurements are susceptible to variations in analytical conditions, these should be suitably controlled, or a precautionary statement should be included in the procedure. One consequence of the evaluation of robustness and ruggedness should be that a series of system suitability parameters isestablished to ensure that the validity of the analytical procedure is maintained whenever used. Typical variations are the stability of analytical solutions, different equipment, and different analysts. In the case of liquid chromatography, typical variations are the pH of the mobile phase, the mobile phase composition, different lots or suppliers of columns, the temperature, and the flow rate. In the case of gas chromatography, typical variations are different lots or suppliers of columns, the temperature, and the flow rate. System suitability tests are based on the concept that the equipment, electronics, analytical operations, and samples to be analyzed constitute an integral system that can be evaluated as such. System suitability test parameters to be established for a particular procedure depend on the type of procedure being evaluated. They are especially important in the case of chromatographic procedures. Submissions to the USP should make note of the requirements under the System Suitability section in the general test chapter Chromatography 621.Data Elements Required for ValidationCompendial test requirements vary from highly exacting analytical determinations to subjective evaluation of attributes. Considering this broad variety, it is only logical that different test procedures require different validation schemes. This chapter covers only the most common categories of tests for which validation data should be required. These categories are as follows:Category I— Analytical procedures for quantitation of major components of bulk drug substances or active ingredients (including preservatives) in finished pharmaceutical products.Category II— Analytical procedures for determination of impurities in bulk drug substances or degradation compounds in finished pharmaceutical products. These procedures include quantitative assays and limit tests.Category III — Analytical procedures for determination of performance characteristics (e.g., dissolution, drug release, etc.).Category IV — Identification tests.For each category, different analytical information is needed. Listed in Table 2 are data elements that are normally required for each of these categories.Table 2. Data Elements Required for ValidationAnalytical Performance Characteristics Category I Category IICategory IIICategory IV Quantitative Limit Tests AccuracyYes Yes **No PrecisionYes Yes No Yes No SpecificityYes Yes Yes *Yes Detection LimitNo No Yes *No Quantitation LimitNo Yes No *No LinearityYes Yes No *No Range Yes Yes **No * May be required, depending on the nature of the specific test. Already established general procedures (e.g., titrimetric determination of water, bacterial endotoxins) should be verified to establish their suitability for use, such as their accuracy (and absence of possible interference) when used for a new product or raw material.When validating physical property methods, consider the same performance characteristics required for any analytical procedure. Evaluate use of the performance characteristics on a case-by-case basis, with the goal ofdetermining that the procedure is suitable for its intended use. The specific acceptance criteria for each validation parameter should be consistent with the intended use of the method.Physical methods may also be classified into the four validation categories. For example, validation of a quantitative spectroscopic method may involveevaluation of Category I or Category II Analytical Performance Characteristics, depending on the method requirements. Qualitative physical propertymeasurements, such as particle size, surface area, bulk and tapped density,which could impact performance characteristics, often best fit in Category III. Category IV Analytical Performance Characteristics usually applies to validation of qualitative identification spectroscopic methods. However, the various techniques may be used for different purposes, and the specific use of the method and characteristics of the material being analyzed should be considered when definitively applying a category to a particular type of method.The validity of an analytical procedure can be verified only by laboratory studies. Therefore, documentation of the successful completion of such studies is a basic requirement for determining whether a procedure is suitable for its intended application(s). Current compendial procedures are also subject to regulations that require demonstration of suitability under actual conditions of use (see Verification of Compendial Procedures 1226for principles relative to the verification of compendial procedures). Appropriate documentation should accompany any proposal for new or revised compendial analytical procedures.contacting USP.Topic/Question Contact Expert CommitteeGeneral Chapter Horacio N. Pappa, Ph.D.Principal ScientificLiaison1-301-816-8319 (GCPA2010) General Chapters - Physical AnalysisUSP34–NF29 Page 778Pharmacopeial Forum: Volume No. 35(2) Page 444。
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a rXiv:n ucl-e x /563v11J un25New precision determination of g P and G F :the MuXperiments at PSI Bernhard Lauss Physics Department,University of California,366LeConte Hall,Berkeley,CA 94720,USA lauss@ on behalf of the MuCAP [1]and MuLAN [2]collaborations We discuss two precision experiments which will measure fundamental weak interaction parameters:MuLAN’s goal is the measurement of the positive muon lifetime to 1ppm,which will in turn determine the Fermi coupling constant G F to 0.5ppm precision.MuCAP is the first experiment which will unambiguously determine the induced pseudoscalar form factor of the proton,g P .While contradictory experimental results for g P are under discussion,firm theoretical calculations on the percent level within the framework of Chiral Perturbation Theory are now challenging the measurements.We will describe our experimental efforts and latest achievements.1Precision determination of G F -the MuLAN experimentWe have seen impressive advances in our precise knowledge of many parameters defining the electroweak interaction within the Standard Model.However,the value of one of the most fundamental weak parameters,the Fermi coupling constant G F ,has not been improved in over two decades (see Fig.1).Usually G F is determined via a measurement of the muon lifetime τµ1192π3F m 2e 5m 2µBernhard Lauss√M 2Z (1+∆r ),(2)with weak radiative corrections being summarized in ∆r[4].The calculated quantity ∆r depends on the entire set of input parameters,e.g.M Z ,M Higgs ,m top ,α.Recently,these calculations were improved to the sub-ppm level by including numerically important QCD and electroweak higher-order terms up to 2-loop level.Therefore a precise comparison between theoretical and experimental values,e.g.for M W (Eq.2)is possible [4].Con-sequently,G F sets important constraints on the Standard Model and SUSY parameters.Furthermore,G F sets the weak scale and is intimately connected to the vacuum expecta-tion value of the Higgs field.The best possible experimental measurement of G F at the present technological limit is therefore highly desirable,as the 18ppm precision limit on the PDG average on τµ[5]is dominated by experimental counting statistics.Figure 1:Progression of positive muon lifetime measurements [5].The 1ppm error goalof MuLAN is too small to be visible on this scale.The MuLAN experiment (Mu on L ifetime AN alysis),intents to measure a total of 1012µ+decays,in order to achieve a 1ppm statistical error in the lifetime.Since the status report on the MuXprogram in [6]we have achieved substantial progress.A modification of the continuous high intensity muon beam line at the Paul Scherrer Institut was neces-sary to enable the collection of 1012events within a reasonable time.We have built an electrostatic kicker which applies an artificial time structure to the DC beam in the πE3area and found a kickable beam tune which provides up to 8MHz of muons.Following a 5µs muon collection period in the target,the kicker deflects the beam for 27µs while muon decays are measured.MuLAN is designed to minimize the systematic errors in several ways:•Muon polarization:The beam muons are highly polarized,and the preferential emission of decay positrons in muon spin direction could cause a position-and time-dependent positron detection efficiency as polarized muons rotate in an external magnetic field.We are currently investigating two specific targets:i)Arnokrome-3(Fig.2b)is a proprietary chromium-cobalt-iron alloy sheet,which,due to an internal field of a few Tesla,precesses muons very fast with respect to muon decay.Therefore polarization effects are negligible.ii)A solid sulfur target which maximizes the depolarization of theBernhard Lauss2m N σµνqν+G S(q2)mµγ5qµ+iG T(q2)m2π−q2−11While the RMC process has a105times lower branching than OMC,the emittedγcan have energies up to100MeV.Therefore theseγ’s come closer to the pion pole and the measurement is in principle four times more sensitive to g P than OMC.Bernhard LaussBernhard Lausshome.html [2]MuLAN Collaboration:T.I.Banks,K.M.Crowe,F.E.Gray,and uss(U.of Cali-fornia,Berkeley and LBNL);R.M.Carey,W.Earle,A.Gafarov,B.Graf,K.R.Lynch,Y.Ma-tus,ler,Q.Peng,and B.L.Roberts(Boston University);D.Chitwood,S.M.Clay-Bernhard Lausshome.html[3]J.Erler and M.Ramsey-Musolf,Prog.Part.Nucl.Phys.54(2005)351.[4]W.Hollik et al.,Acta Phys.Polon.B35(2004)2711.[5]S.Eidelmann et al.,Phys.Lett.B592(2004)1.[6]P.Kammel,Proc.of the Int.Workshop on Exotic Atoms-Future Perspectives,EXA’02,published by the Austrian Academy of Sciences Press,Vienna2003.[7]S.Weinberg,Phys.Rev.112(1958)1375.[8]V.Bernard,N.Kaiser,U.-G.Meissner,Phys.Rev.D50(1994)6889,andV.Bernard,L.Elouadrhiri,U.-G.Meissner,J.Phys.G28(2002)R1.[9]aerts and J.-L.Lucio-Martinez,Nucl.Phys.A678(2000)110.[10]G.Bardin et al.,Nucl.Phys.A352(1981)365.[11]P.Ackerbauer et al.,Phys.Lett.B417(1998)224.[12]G.Jonkmans et al.,Phys.Rev.Lett.77(1996)4512.[13]T.Gorringe and H.W.Fearing,Rev.Mod.Phys.76(2004)31.[14]G.Bardin et al.,Phys.Lett.104B(1981)320.[15]The TRIUMF RMC group(D.Armstrong et al.)has not yet released theirfinal resulton theλOP measurement.At the APS2004spring meeting in Denver,CO(USA),the following values have been presented,depending on thefinal deuterium concentration in the protium target:λOP=13.8±1.6×10−4s−1(for maximum estimated D2 contamination),andλOP=12.2±1.6×10−4s−1(for no D2presence).[16]D.D.Bakalov et al.,Nucl.Phys.A384(1982)302.[17]P.Kammel.Internal MuCAP Note29,2003.[18]uss,P.Kammel,A.Vasilyev,Internal MuCAP Note30,2005.[19]A.Vasilyev et al.,Proceedings of the“NHA Annual Hydrogen Conference2005”,Washington DC,USA,March2005.[20]P.Kammel,Hyp.Int.118(1999)323.。