课外阅读一阿司匹林及其片剂的质量标准(USP) Aspirin CHO4180.16 Benzoic acid, 2-(acetyloxy)-Salicylic acid acetate 50-78-2 >>Aspirin contains not less than 99.5 percent and not more than 100.5 percent of CgHg O4, calculated on the dried basis Packaging and storage-Preserve in tight containers USP Reference standards -USP Aspirin RS. Identification A: Heat it with water for several minutes, cool, and add l or 2 drops of ferric chloride ts: a violet-red color is produced B: Infrared Absorption Loss on drying -Dry it over silica gel for 5 hours: it loses not more than 0.5% of its weight Readily carbonizable substances -Dissolve 500mg in 5 mL of sulfuric acid TS: the solution has no more color than Matching Fluid Q Residue on ignition : not more than 0.05% Substances insoluble in sodium carbonate Ts-A solution of 500mg in 10 mL of warm sodium carbonate TS is clear Chloride -Boil 1 5g with 75 mL of water for 5 minutes, cool, add sufficient water to restore the original volume, and filter. A 25-mL portion of the filtrate shows no more chloride than corresponds to 0. 10 mL of 0.020n hydrochloric acid (0.014%) Sulfate-Dissolve 60g in 37 mL of acetone, and add 3 mL of water. Titrate potentiometrically with 0.02 M lead perchlorate prepared by dissolving 9.20 g of lead perchlorate in water to make 1000mL of solution, using a pH meter capable of a minimum reproducibility of +0. 1 mV(see pH )equipped with an electrode system consisting of a lead-specific electrode and a silver-silver chloride reference glass-sleeved electrode containing a solution of tetraethylammonium perchlorate in glacial cetic acid (1 in 44)(see Titrimetry ): not more than 1. 25mL of 0.02 M lead perchlorate is consumed(0.04%). NOTE After use, rinse the lead-specific electrode with water, drain the reference electrode, flush with water, rinse with methanol and allow to dry. I Heavy metals-Dissolve 2 g in 25 mL of acetone, and add I mL of water. Add 1.2 mL of thioacetamide-glycerin base ts and 2 mL of pH 3.5 Acetate Buffer(see Heavy Metals ), and allow to stand for 5 minutes: any color produced is not darker than that of a control made with 25 mL of acetone and 2 mL of Standard Lead Solution(see Heavy Metals ), treated in the same manner. The limit is 10ug per g
课外阅读一 阿司匹林及其片剂的质量标准（USP） Aspirin O O H 3C HO O C9H8O4 180.16 Benzoic acid, 2(acetyloxy)Salicylic acid acetate [50782]. >>Aspirin contains not less than 99.5 percent and not more than 100.5 percent of C9H8O4, calculated on the dried basis. Packaging and storagePreserve in tight containers. USP Reference standards －USP Aspirin RS. Identification－ A: Heat it with water for several minutes, cool, and add 1 or 2 drops of ferric chloride TS: a violetred color is produced. B: Infrared Absorption Loss on drying －Dry it over silica gel for 5 hours: it loses not more than 0.5% of its weight. Readily carbonizable substances －Dissolve 500mg in 5 mL of sulfuric acid TS: the solution has no more color than Matching Fluid Q. Residue on ignition : not more than 0.05%. Substances insoluble in sodium carbonate TS－A solution of 500mg in 10 mL of warm sodium carbonate TS is clear. Chloride －Boil 1.5g with 75 mL of water for 5 minutes, cool, add sufficient water to restore the original volume, and filter. A 25mL portion of the filtrate shows no more chloride than corresponds to 0.10 mL of 0.020 N hydrochloric acid (0.014%). SulfateDissolve 6.0g in 37 mL of acetone, and add 3 mL of water. Titrate potentiometrically with 0.02 M lead perchlorate, prepared by dissolving 9.20 g of lead perchlorate in water to make 1000mL of solution, using a pH meter capable of a minimum reproducibility of ±0.1 mV (see pH ) equipped with an electrode system consisting of a leadspecific electrode and a silversilver chloride reference glasssleeved electrode containing a solution of tetraethylammonium perchlorate in glacial acetic acid （1 in 44）(see Titrimetry ): not more than 1.25mL of 0.02 M lead perchlorate is consumed (0.04%). [NOTE －After use, rinse the leadspecific electrode with water, drain the reference electrode, flush with water, rinse with methanol, and allow to dry.] Heavy metals－Dissolve 2 g in 25 mL of acetone, and add 1 mL of water. Add 1.2 mL of thioacetamideglycerin base TS and 2 mL of pH 3.5 Acetate Buffer(see Heavy Metals ), and allow to stand for 5 minutes: any color produced is not darker than that of a control made with 25 mL of acetone and 2 mL of Standard Lead Solution (see Heavy Metals ), treated in the same manner. The limit is 10μg per g
Limit of free salicylic acid- Dissolve 2.5g in sufficient alcohol to make 25.0 mL. To each of two matched color-comparison tubes add 48 mL of water and l mL of a freshly prepared, diluted ferric ammonium sulfate solution( prepared by adding 1 mL of I N hydrochloric acid to 2 mL of ferric ammonium sulfate TS and diluting with water to 100 mL). Into one tube pipet l mL of a standard solution of salicylic acid in water, containing 0. 10 mg of salicylic acid per mL. Into the second tube pipet 1 mL of the I in 10 solution of Aspirin. Mix the contents of each tube: after 30 seconds, the color in the second tube is not more intense than that in the tube containing the salicylic acid(0. 1%) Organic volatile impurities, Method lv : meets the requirements Assay-Place about 1, 5g of Aspirin, accurately weighed, in a flask, add 50.0 mL of 0.5 N sodium hydroxide vs, and boil the mixture gently for 10 minutes. Add phenolphthalein TS, and titrate the excess sodium hydroxide with 0.5N sulfuric acid Vs Perform a blank determination(see Residual Titrations under Titrimetry). Each mL of 0.5 N sodium hydroxide is equivalent to 45.04 mg of C9HgO4 Aspirin Tablets > Aspirin Tablets contain not less than 90.0 percent and not more than 110.0 percent of the labeled amount of C9HgO4. Tablet of larger than &1-mg size contain no sweeteners or other flavors NOTE-Tablets that are enteric-coated meet the requirements for Aspirin Delayed-release Tablets Packaging and storage-Preserve in tight containers. Preserve flavored or sweetened Tablets of 81-mg size or smaller in containers holding not more than 36 Tablets each USP Reference standards -USP Aspirin RS. USP Salicylic Acid RS. Identification- A: Crush I Tablet, boil it with 50 mL of water for 5 minutes, cool, and add I or 2 drops of ferric chloride TS: a violet-red color B: Infrared absorption -Prepare the test specimen as follows. Shake a quantity of finely powdered Tablets, equivalent to about 500 mg of aspirin, with 10 mL of alcohol for several minutes. Centrifuge the mixture. Pour off the clear supernatant liquid, and evaporate it to dryness. Dry the residue in vacuum at 60C for 1 hour Dissolution <711 Medium: 0.5 M acetate buffer, prepared by mixing 2.99 g of sodium acetate trihydrate and 1.66 mL of glacial acetic acid with water to obtain 1000mL of solution having a pH of 4.50+0.05; 500 mL Apparatus 1: 50 rpm Time: 30 minutes Procedure-Determine the amount of Coho dissolved from ultraviolet absorbances at the wavelength of the isosbestic oint of aspirin and salicylic acid at 265 t 2nm of filtered portions of the solution under test, suitably diluted with Dissolution Medium. if necessary, in comparison with a Standard solution having a known concentration of USP Aspirin rs in the same
Limit of free salicylic acid－Dissolve 2.5g in sufficient alcohol to make 25.0 mL. To each of two matched colorcomparison tubes add 48 mL of water and 1 mL of a freshly prepared, diluted ferric ammonium sulfate solution (prepared by adding 1 mL of 1 N hydrochloric acid to 2 mL of ferric ammonium sulfate 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 1 mL 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 more intense than that in the tube containing the salicylic acid (0.1%). Organic volatile impurities, Method IV : meets the requirements. Assay－Place about 1.5g of Aspirin, accurately weighed, in a flask, add 50.0 mL of 0.5 N sodium hydroxide VS, and boil the mixture gently for 10 minutes. Add phenolphthalein TS, and titrate the excess sodium hydroxide with 0.5 N sulfuric acid VS. Perform a blank determination (see Residual Titrations under Titrimetry ). Each mL of 0.5 N sodium hydroxide is equivalent to 45.04 mg of C9H8O4. Aspirin Tablets >> Aspirin Tablets contain not less than 90.0 percent and not more than 110.0 percent of the labeled amount of C9H8O4. Tablets of larger than 81mg size contain no sweeteners or other flavors. NOTETablets that are entericcoated meet the requirements for Aspirin Delayedrelease Tablets. Packaging and storagePreserve in tight containers. Preserve flavored or sweetened Tablets of 81mg size or smaller in containers holding not more than 36 Tablets each. USP Reference standards USP Aspirin RS. USP Salicylic Acid RS. Identification A: Crush 1 Tablet, boil it with 50 mL of water for 5 minutes, cool, and add 1 or 2 drops of ferric chloride TS: a violetred color is produced. B: Infrared absorption Prepare the test specimen as follows. Shake a quantity of finely powdered Tablets, equivalent to about 500 mg of aspirin, with 10 mL of alcohol for several minutes. Centrifuge the mixture. Pour off the clear supernatant liquid, and evaporate it to dryness. Dry the residue in vacuum at 60℃ for 1 hour. Dissolution Medium: 0.5 M acetate buffer, prepared by mixing 2.99 g of sodium acetate trihydrate and 1.66 mL of glacial acetic acid with water to obtain 1000mL of solution having a pH of 4.50±0.05; 500 mL. Apparatus 1 : 50 rpm. Time: 30 minutes. Procedure－Determine the amount of C9H8O4 dissolved from ultraviolet absorbances at the wavelength of the isosbestic point of aspirin and salicylic acid at 265±2nm of filtered portions of the solution under test, suitably diluted with Dissolution Medium. if necessary, in comparison with a Standard solution having a known concentration of USP Aspirin RS in the same
medium. [ NoTE-Prepare the Standard solution at the time of use. An amount of alcohol not to exceed 1% of the total volume of the Standard solution may be used to bring the Reference Standard into solution prior to dilution with Dissolution Medium. Tolerances-Not less than 80%(Q)of the labeled CgHgO4 is dissolved in 30 minutes Uniformity of dosage units : meet the requirements Limit of free salicylic acid Mobile phase and diluting Solution-Prepare as directed in the Assay. Standard solution-Dissolve an accurately weighed quantity of USP Salicylic Acid RS in the Standard preparation prepared as directed in the Assay, to obtain a solution having a known concentration of about 0.015 mg of salicylic acid per mL Test preparation-Use the Stock solution prepared as directed for Assay preparation in the assay Chromatographic system-Use the Chromatographic system described in the Assay Chromatograph the Standard solution and record the peak responses as directed under procedure in the Assay. The relative standard deviation of the salicylic acid peak responses is not more than 4.0%. In a suitable chromatogram, the resolution, R, between salicylic acid and aspirin is not less than 2.0 Procedure- Proceed as directed for Procedure in the Assay. The relative retention times are about 0.7 for salicylic acid and 1.0 for aspirin. Calculate the percentage of salicylic acid(C7H6O3) in the portion of Tablets taken by the formula 2000C/Q4(r/r;), n which C is the concentration, in mg per mL, of USP Salicylic Acid RS in the Standard solution, @a is the quantity, in mg, of aspirin(C9H8O4) in the portion of Tablets taken, as determined in the Assay, and ro and rs are the peak responses of the salicylic acid peaks obtained from the Test preparation and the Standard solution, respectively: not more than 3.0% is found. In the case that are coated not more than 3. 0% is found A Mobile phase-Dissolve 2 g of sodium l-heptanesulfonate in a mixture of 850 mL of water and 150 mL of acetonitrile, and adjust with glacial acetic acid to a pH of 3.4 Diluting solution-Prepare a mixture of acetonitrile and formic acid (99: 1) Standard preparation-Dissolve an accurately weighed quantity of USP Aspirin rs in Diluting solution to obtain a solution having a known concentration of about 0.5 mg per mL Assay preparation-Weigh and finely powder not less than 20 Tablets. Transfer an accurately weighed quantity of the powder, equivalent to about 100 mg of aspirin, to a suitable container. Add 20.0 mL of Diluting solution and about 10 glass beads. Shake vigorously for about 10 minutes, and centrifuge(stock solution). Quantitatively dilute an accurately measured volume of the Stock solution with 9 volumes of Diluting solution(Assay preparation). Retain the remaining portion of Stock solution for the test for Limit of salicylic acid. Chromatographic system(see Chromatography )-The liquid chromatograph is equipped with a 280-nm detector and a 4.0-mmX30-cm column containing packing Ll, The flow rate is about 2 mL per minute. Chromatograph the standard
medium. [NOTEPrepare the Standard solution at the time of use. An amount of alcohol not to exceed 1% of the total volume of the Standard solution may be used to bring the Reference Standard into solution prior to dilution with Dissolution Medium.] TolerancesNot less than 80% (Q) of the labeled C9H8O4 is dissolved in 30 minutes. Uniformity of dosage units : meet the requirements Limit of free salicylic acid Mobile phase and Diluting SolutionPrepare as directed in the Assay. Standard solutionDissolve an accurately weighed quantity of USP Salicylic Acid RS in the Standard preparation prepared as directed in the Assay, to obtain a solution having a known concentration of about 0.015 mg of salicylic acid per mL. Test preparationUse the Stock solution prepared as directed for Assay preparation in the Assay. Chromatographic systemUse the Chromatographic system described in the Assay. Chromatograph the Standard solution, and record the peak responses as directed under Procedure in the Assay. The relative standard deviation of the salicylic acid peak responses is not more than 4.0%. In a suitable chromatogram, the resolution, R, between salicylic acid and aspirin is not less than 2.0. ProcedureProceed as directed for Procedure in the Assay. The relative retention times are about 0.7 for salicylic acid and 1.0 for aspirin. Calculate the percentage of salicylic acid (C7H6O3) in the portion of Tablets taken by the formula: 2000(C/QA)（ru/rs）， in which C is the concentration, in mg per mL, of USP Salicylic Acid RS in the Standard solution, QA is the quantity, in mg, of aspirin (C9H8O4) in the portion of Tablets taken, as determined in the Assay, and rυ and rs are the peak responses of the salicylic acid peaks obtained from the Test preparation and the Standard solution, respectively: not more than 3.0% is found. In the case that are coated, not more than 3.0% is found. Assay Mobile phaseDissolve 2 g of sodium 1heptanesulfonate in a mixture of 850 mL of water and 150 mL of acetonitrile, and adjust with glacial acetic acid to a pH of 3.4. Diluting solutionPrepare a mixture of acetonitrile and formic acid (99:1). Standard preparationDissolve an accurately weighed quantity of USP Aspirin RS in Diluting solution to obtain a solution having a known concentration of about 0.5 mg per mL. Assay preparationWeigh and finely powder not less than 20 Tablets. Transfer an accurately weighed quantity of the powder, equivalent to about 100 mg of aspirin, to a suitable container. Add 20.0 mL of Diluting solution and about 10 glass beads. Shake vigorously for about 10 minutes, and centrifuge (stock solution). Quantitatively dilute an accurately measured volume of the Stock solution with 9 volumes of Diluting solution (Assay preparation). Retain the remaining portion of Stock solution for the test for Limit of salicylic acid. Chromatographic system (see Chromatography )－The liquid chromatograph is equipped with a 280nm detector and a 4.0mm×30cm column containing packing L1. The flow rate is about 2 mL per minute. Chromatograph the Standard
preparation, and record the peak responses as directed under Procedure: the relative standard deviation is not more than 2.0% In a suitable chromatogram, the tailing factor is not greater than 2.0 Procedure-Separately inject equal volumes(about 10uL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of aspirin( C9HgO4) in the portion of Tablets taken by the formula 200C(r/r in which C is the concentration, in mg per mL, of USP Aspirin RS in the Standard preparation, and ro and Is are the pea responses of the aspirin peaks obtained from the Assay preparation and the standard preparation, respectively
preparation, and record the peak responses as directed under Procedure: the relative standard deviation is not more than 2.0%. In a suitable chromatogram, the tailing factor is not greater than 2.0. ProcedureSeparately inject equal volumes (about 10mL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of aspirin (C9H8O4) in the portion of Tablets taken by the formula: 200C(rυ/rs), in which C is the concentration, in mg per mL, of USP Aspirin RS in the Standard preparation, and rυ and rs are the peak responses of the aspirin peaks obtained from the Assay preparation and the Standard preparation, respectively