bp2010.利福平

British Pharmacopoeia Volume I & II Monographs: Medicinal and Pharmaceutical Substances General Notices (Ph Eur monograph 0052) C43H58N4O12 823 13292-46-1 Action and use Rifamycin antituberculosis drug. Preparations Rifampicin Capsules Rifampicin Oral Suspension Ph Eur DEFINITION (2S,12Z,14E,16S,17S,18R,19R,20R,21S,22R,23S,24E)-5,6,9,17,19-Pentahydroxy-23-methoxy-2,4,12,16,18,20,22- heptamethyl-8-[[(4-methylpiperazin-1-yl)imino]methyl]-1,11-dioxo-1,2-dihydro-2,7-(epoxypentadeca[1,11,13] trienimino)naphto[2,1-b]furan-21-yl acetate. Semisynthetic antibiotic obtained from rifamycin SV. Content 97.0 per cent to 102.0 per cent (dried substance). CHARACTERS Appearance Reddish-brown or brownish-red, crystalline powder. Solubility Slightly soluble in water, soluble in methanol, slightly soluble in acetone and in ethanol (96 per cent). IDENTIFICATION A. Ultraviolet and visible absorption spectrophotometry (2.2.25). Test solution Dissolve 50 mg in 50 ml of methanol R. Dilute 1 ml of this solution to 50 ml with phosphate buffer solution pH 7.4 R. Rifampicin 页码，1/4Rifampicin 2013-4-4mk:@MSITStore:D:\罗飞\GMP\仪器验证\TOC(总有机碳器)\bp2010.chm::/... PDF 文件使用 "pdfFactory Pro" 试用版本创建 www.fineprint.cn Spectral range 220-500 nm. Absorption maxima At 237 nm, 254 nm, 334 nm and 475 nm. Absorbance ratio A334/A475 = about 1.75. B. Infrared absorption spectrophotometry (2.2.24). Preparation Mulls in liquid paraffin R. Comparison rifampicin CRS. C. Suspend about 25 mg in 25 ml of water R, shake for 5 min and filter. To 5 ml of the filtrate add 1 ml of a 100 g/l solution of ammonium persulphate R in phosphate buffer solution pH 7.4 R and shake for a few minutes. The colour changes from orange-yellow to violet-red and no precipitate is formed. TESTS pH (2.2.3) 4.5 to 6.5 for a 10 g/l suspension in carbon dioxide-free water R. Related substances Liquid chromatography (2.2.29). Prepare the test solution and the reference solution immediately before use. Solvent mixture To 10 volumes of a 210.1 g/l solution of citric acid R add 23 volumes of a 136.1 g/l solution of potassium dihydrogen phosphate R, 77 volumes of a 174.2 g/l solution of dipotassium hydrogen phosphate R, 250 volumes of acetonitrile R and 640 volumes of water R. Test solution Dissolve 20.0 mg of the substance to be examined in acetonitrile R and dilute to 10.0 ml with the same solvent. Dilute 5.0 ml of this solution to 50.0 ml with the solvent mixure. Reference solution Dissolve 20.0 mg of rifampicin quinone CRS (impurity A) in acetonitrile R and dilute to 100.0 ml with the same solvent. To 1.0 ml of this solution add 1.0 ml of the test solution and dilute to 100.0 ml with the solvent mixture. Column: — size: l = 0.12 m, Ø = 4.6 mm; — stationary phase: octylsilyl silica gel for chromatography R (5 µm). Mobile phase Mix 35 volumes of acetonitrile R and 65 volumes of a solution containing 0.1 per cent V/V of phosphoric acid R, 1.9 g/l of sodium perchlorate R, 5.9 g/l of citric acid R and 20.9 g/l of potassium dihydrogen phosphate R. Flow rate 1.5 ml/min. Detection Spectrophotometer at 254 nm. Injection 20 µl. Run time Twice the retention time of rifampicin. System suitability Reference solution: — resolution: minimum 4.0 between the peaks due to rifampicin and impurity A; if necessary, adjust the concentration of acetonitrile in the mobile phase. Limits: — impurity A: not more than 1.5 times the area of the corresponding peak in the chromatogram obtained with the reference solution (1.5 per cent); — any other impurity: for each impurity, not more than the area of the peak due to rifampicin in the chromatogram obtained with the reference solution (1.0 per cent); 页码，2/4Rifampicin 2013-4-4mk:@MSITStore:D:\罗飞\GMP\仪器验证\TOC(总有机碳分析器)\bp2010.chm::/... PDF 文件使用 "pdfFactory Pro" 试用版本创建 www.fineprint.cn — sum of impurities other than A: not more than 3.5 times the area of the peak due to rifampicin in the chromatogram obtained with the reference solution (3.5 per cent); — disregard limit: 0.05 times the area of the peak due to rifampicin in the chromatogram obtained with the reference solution (0.05 per cent). Heavy metals (2.4.8) Maximum 20 ppm. 1.0 g complies with test C. Prepare the reference solution using 2 ml of lead standard solution (10 ppm Pb) R. Loss on drying (2.2.32) Maximum 1.0 per cent, determined on 1.000 g by drying at 80 °C at a pressure not exceeding 0.67 kPa for 4 h. Sulphated ash (2.4.14) Maximum 0.1 per cent, determined on 2.0 g. ASSAY Dissolve 0.100 g in methanol R and dilute to 100.0 ml with the same solvent. Dilute 2.0 ml of this solution to 100.0 ml with phosphate buffer solution pH 7.4 R. Measure the absorbance (2.2.25) at the absorption maximum at 475 nm, using phosphate buffer solution pH 7.4 R as the compensation liquid. Calculate the content of C43H58N4O12, taking the specific absorbance to be 187. STORAGE Under nitrogen in an airtight container, protected from light, at a temperature not exceeding 25 °C. IMPURITIES Specified impurities A. Other detectable impurities (The following substances would, if present at a sufficient level, be detected by one or other of the tests in the monograph. They are limited by the general acceptance criterion for other/unspecified impurities and/or by the general monograph Substances for pharmaceutical use (2034). It is therefore not necessary to identify these impurities for demonstration of compliance. See also 5.10. Control of impurities in substances for pharmaceutical use): B. A. rifampicin quinone, 页码，3/4Rifampicin 2013-4-4mk:@MSITStore:D:\罗飞\GMP\仪器验证\TOC(总有机碳分析器)\bp2010.chm::/... PDF 文件使用 "pdfFactory Pro" 试用版本创建 www.fineprint.cn B. rifampicin N-oxide. Ph Eur © Crown Copyright 2009 页码，4/4Rifampicin 2013-4-4mk:@MSITStore:D:\罗飞\GMP\仪器验证\TOC(总有机碳分析器)\bp2010.chm::/... PDF 文件使用 "pdfFactory Pro" 试用版本创建 www.fineprint.cn