WHO-富马酸替诺福韦Tenofovir_disoproxil_fumarate质量标准.doc

Monographs: Pharmaceutical substances: Tenofoviri disoproxili fumaras - Tenofovir disoproxil fumarate C19H30N5O10P,C4H4O4 Relative molecular mass. 635.5 Chemical name. 1,1-bis(1-methylethyl) 1,1-[({[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl}phosphonoyldioxy)dimethyl] dicarbonate (ester) hydrogen (2E)-but-2-enedioate (salt); CAS Reg.No. 202138-50-9. Description. White to almost-white, crystalline powder. Solubility. Slightly soluble in water, soluble in methanol, very slightly soluble in dichloromethane. Category. Antiretroviral (Nucleotide Reverse Transcriptase Inhibitor). Storage. Tenofovir disoproxil fumarate should be kept in a tightly closed container, protected from light, and stored at a temperature between 2 and 8°C. Additional information. Tenofovir disoproxil fumarate may exhibit polymorphism. Requirements Definition. Tenofovir disoproxil fumarate contains not less than 98.5 percent and not more than 101.0 percent of tenofovir disoproxil fumarate (C19H30N5O10P,C4H4O4), calculated with reference to the anhydrous substance. Manufacture. The production method is validated to ensure that the substance, if tested, would comply with:- a limit of not more than 5 ppm for the mutagenic impurity 9-(prop-1-enyl)-9H-purin-6-amine (impurity K), which may be a synthesis related substance, using a suitable method, and- a limit of not more than 1.0% for the tenofovir disoproxil (S)-enantiomer (impurity G), using a suitable chiral chromatographic method. Identity tests ? Either tests A, B and C or test D may be applied. A. Carry out test A.1 or, where UV detection is not available, test A.2. A.1 Carry out the test as described under 1.14.1 Thin-layer chromatography, using silica gel R6 as the coating substance and a mixture of 67 volumes of dichloromethane R, 20 volumes of acetonitrile R, 10 volumes of methanol R and 3 volumes of ammonia (~260 g/l) TS as the mobile phase. Apply separately to the plate 5 μl of each of 2 solutions in methanol containing (A) 10 mg