Evaluation Method Research Of Quality For Nedaplatin

The application and research of platinum anti-cancer drugs have got unprecedented development since cis-platinum was found to have good anti-cancer activity in the year of1967. At present, this kind of drugs has been considered to be indispensable in cancer chemotherapies, which occupied bout70%-80%of all the cancer chemotherapies in China. Currently, cisplatin, carboplatin, oxaliplatin and Nedaplatin are applied in clinic in our country as the important platinum drugs, among which the first three drugs have been given more attention, and their quality standards have been included in USP37, BP2014, EP8.0and Chinese pharmacopoeia of the2010version or its supplement. Consequently, we compared the quality standards of these three drugs in this paper. In addition, there are a few of the references regarding Nedaplatin (cis-glycolic acid-diamine platinum) and the quality standard of Nedaplatin has not been included in any of the above pharmacopoeias. So far, the quality standard of Nedaplatin has always been individual YBH standard for each enterprise since it has been approved to be listed in China in2004. Our institute started standard research according to the raising standard requirement of national pharmacopoeia commission from the year of2010. Therefore, quality method research of Nedaplatin was chosen to be the main content of this paper.In this paper, a kind of determination method about related substances and assay of Nedaplatin were established. With octadecyl silane bonded silica used as filler (SHISEIDO CAPCELL PAK C18SG1205μm4.6×250mm. CAPCELL PAK C18MG Ⅱ5μm4.6×250mm or CAPCELL PAK C18MG Ⅲ5μm4.6×250mm or equally authentic column), octane sulfonic acid sodium solution (dissolve0.856g octane sulfonic acid sodium in water, add phosphoric acid0.5ml, and dilute to1000ml by water)-acetonitrile (91:9) used as the mobile phase, flow rate was1.0ml/min, column temperature was40℃, and the detection wavelength was220nm. Nedaplatin showed good linearity in the concentration range of0.025-4.000mg/ml (correlation coefficient R=0.9998). The detection limit was0.05036μg/ml, the repeatability was0.9%(n=6) and the recovery rate was98.9%(n=9, RSD=0.4%).The determination method of related substances and assay of Nedaplatin established in this paper has been jointly verified by our institute, the review institute and the manufacturing enterprises. The specificity, accuracy, repeatability, detection limit, quantitation limit, linearity and durability are in line with the requirements. This method solves the problems of specificity and durability which have disturbed the enterprise for years by effectively separating the related substances and the main component Nedaplatin. The method is simple, accurate and applicable to the quality control of this product, and the method can be used as an official standard.