The Quality Research Of The Quality Research Of Amikacin Sulfate And Its Injection

This subject for the national drug quality standards was issued by the Chinese ministry of health- the gates foundation tuberculosis control project(phase II). The objective of this study was to improve the quality standards of amikacin sulfate and its injection. It provides a scientific basis for increasing and revising the quality control project of Chinese Pharmacopoeia.The first part of the thesis develops a derivatization HPLC method for the determination of the related substances and content of amikacin sulfate and its injection. Chromatographic behavior of amikacin sulfate and impurities were studied. Meanwhile, the study investigates and selects the optimum conditions of the related substances method, gradient elution program,sample volume and the control of kanamycin, and establishes the methodology validation.The second part develops a new HPLC- charged aerosol detector technology for the determination of kanamycin and sulfate in amikacin sulfate, and achieves the higher sensitivity. The optimal chromatography conditions of HPLC-CAD were studied, and the methodology validation was established.The third part develops a HPLC-ESI-MSn method for separating and identifying the impurities in amikacin sulfate. The structures of the nine impurities were deduced based on the HPLC-MSn data by use of electrospray ion trap mass spectrometry in the multi-stage MS full scan mode. There were three new impurities(impurityⅠ 、 impurityⅡ 、mpurityⅢ),and a discipline of mass fragmentation patterns and structural assignment of these impurities were studied.The fourth part develops the cytotoxicity of five impurities of amikacin sulfate in vitro on fibroblast with MTT method, and evaluates the impurities of Amikacin sulfate on the cytotoxicity of fibroblast cells.