USP 35阿司匹林原料药质量标准

USP 35

Official Monographs / Aspirin 2245

W = weight of Sample (mg)

•USP R EFERENCE S TANDARDS 〈11〉Acceptance criteria: 98.5%–101.5% on the dried basis USP Aspartic Acid RS

IMPURITIES

•R ESIDUE ON I GNITION 〈281〉: NMT 0.1%•C HLORIDE AND S ULFATE , Chloride 〈221〉

Sample solution: Dissolve 0.7 g of Aspartic Acid in 10 mL Aspirin

of diluted nitric acid, and dilute with water to 15 mL.Acceptance criteria: The Sample solution shows no more chloride than corresponds to 0.20 mL of 0.020 N hydrochloric acid (NMT 0.02%).

•C HLORIDE AND S ULFATE , Sulfate 〈221〉

Sample solution: Dissolve 0.8 g of Aspartic Acid in 4 mL of hydrochloric acid, and dilute with water to 15 mL.

C 9H 8O 4180.16

Acceptance criteria: The Sample solution shows no more Benzoic acid, 2-(acetyloxy)-.

sulfate than corresponds to 0.25 mL of 0.020 N sulfuric acid Salicylic acid acetate [50-78-2].

(NMT 0.03%).

•I RON 〈241〉: NMT 10 ppm

» Aspirin contains not less than 99.5 per cent and •H EAVY M ETALS , Method II 〈231〉: NMT 10 ppm not more than 100.5 per cent of C 9H 8O 4, calcu-•C HROMATOGRAPHIC P URITY

System suitability solution: 10 mg each of USP Aspartic lated on the dried basis.

Acid RS and glutamic acid in 2 mL of ammonia TS. Dilute Packaging and storage—Preserve in tight containers.with water to 25.0 mL.

Standard solution: Transfer 5 mg of USP Aspartic Acid RS to USP Reference standards 〈11〉—a 100-mL volumetric flask, dissolve in 2 mL of 17%USP Aspirin RS ammonia solution (prepared by diluting ammonium Identification—

hydroxide, 6 in 10), and dilute with water to volume.

Sample solution: Transfer 0.1 g of Aspartic Acid to a 10-mL A: Heat it with water for several minutes, cool, and add 1 or volumetric flask, dissolve in 2 mL of 17% ammonia solution 2 drops of ferric chloride TS: a violet-red color is produced.(prepared by diluting ammonium hydroxide, 6 in 10), and B: Infrared Absorption 〈197K 〉.

dilute with water to volume.Loss on drying 〈731〉—Dry it over silica gel for 5 hours: it Chromatographic system

loses not more than 0.5% of its weight.

(See Chromatography 〈621〉, Thin-Layer Chromatography .)Readily carbonizable substances 〈271〉—Dissolve 500 mg in Mode: TLC

5 mL of sulfuric acid : the solution has no more color than Adsorbent: 0.25-mm layer of chromatographic silica gel Matching Fluid Q.

mixture

Application volume: 5 µL

Residue on ignition 〈281〉: not more than 0.05%.

Developing solvent system: Butyl alcohol, glacial acetic Substances insoluble in sodium carbonate TS—A solution acid, and water (3:1:1)

of 500 mg in 10 mL of warm sodium carbonate TS is clear.Spray reagent: 2 mg/mL of ninhydrin in a mixture of butyl Chloride 〈221〉—Boil 1.5 g with 75 mL of water for 5 minutes,alcohol and 2N acetic acid (95:5)cool, add sufficient water to restore the original volume, and System suitability

filter. A 25-mL portion of the filtrate shows no more chloride Sample: System suitability solution

than corresponds to 0.10 mL of 0.020 N hydrochloric acid Suitability requirement: The chromatogram of the System (0.014%).

suitability solution exhibits two clearly separated spots.Sulfate —Dissolve 6.0 g in 37 mL of acetone, and add 3 mL of Analysis

water. Titrate potentiometrically with 0.02 M lead per chlorate,Samples: System suitability solution , Standard solution , and prepared by dissolving 9.20 g of lead per chlorate in water to Sample solution

make 1000 mL of solution, using a pH meter capable of a mini-Proceed as directed in the chapter, except dr y the plate at mum reproducibility of ±0.1 mV (see pH 〈791〉) and equipped 80° for 30 min, spray with Spray reagent , and heat at 80°with an electrode system consisting of a lead-specific electrode for 30 min. Examine the plate under white light.

and a silver–silver chloride reference glass-sleeved electrode

Acceptance criteria: No secondar y spot from the Sample containing a solution of tetraethylammonium per chlorate in gla-solution is larger or more intense than the principal spot cial acetic acid (1 in 44) (see Titrimetry 〈541〉): not more than from the Standard solution .

1.25 mL of 0.02 M lead per chlorate is consumed (0.04%).Individual impurities: NMT 0.5%[NOTE —After use, rinse the lead-specific electrode with water,Total impurities: NMT

2.0%drain the reference electrode, flush with water, rinse with meth-anol, and allow to dr y.]

SPECIFIC TESTS

•O PTICAL R OTATION , Specific Rotation 〈781S 〉

Heavy metals—Dissolve 2g in 25 mL of acetone, and add 1Sample solution: 80 mg/mL in 6N hydrochloric acid mL of water. Add 1.2 mL of thioacetamide–glycerin base TS

Acceptance criteria: +24.0° to +26.0°, at 20°

and 2 mL of pH 3.5 Acetate Buffer (see Heavy Metals 〈231〉), and •L OSS ON D RYING 〈731〉: Dry a sample at 105° for 3 h: it loses allow to stand for 5 minutes: any color produced is not darker NMT 0.5% of its weight.than that of a control made with 25 mL of acetone and 2 mL of Standard Lead Solution (see Heavy Metals 〈231〉), treated in ADDITIONAL REQUIREMENTS

the same manner. The limit is 10 µg per g.

•P ACKAGING AND S TORAGE : Preserve in well-closed containers,Limit of free salicylic acid—Dissolve 2.5 g in sufficient alco-and store protected from light.

hol to make 25.0 mL. T o each of two matched color-compari-son tubes add 48 mL of water and 1 mL of a freshly prepared,diluted ferric ammonium sulfate solution (prepared by adding 1mL of 1N hydrochloric acid to 2 mL of ferric ammonium sul-fate TS and diluting with water to 100 mL). Into one tube pipet 1 mL of a standard solution of salicylic acid in water, containing 0.10 mg of salicylic acid per mL. Into the second tube pipet 1mL of the 1 in 10 solution of Aspirin. Mix the contents of each tube: after 30 seconds, the color in the second tube is not