Research Of Impurity Analyses Of Nitroimidazoles

Pharmaceuticals are sort of special commodity in relation to people’s health and even lives, so their quality control has great significance. The safety of a pharmaceutical product is dependent not only on the toxicological properties of the active drug substance itself, but also on the impurities that it contains. Therefore, research on the already exist and may-exist impurities in pharmaceuticals is a key to drug quality control. In this paper, with the help of modern technology, the impurities of nitroimidazoles were studied.The first part of this paper did study on the related substance of ornidazole and sodium chloride injection. It started from the detection of an impurity in this injection by HPLC, then HPLC-QTOF/MS was adopted to analyze the structure of the impurity (named as impurity Ⅱ). Meanwhile, impurity Ⅱ was prepared by pre-HPLC, and its structure was further confirmed by NMR as1-(3-hydroxy-2-hydroxypropyl)-2-methyl-5-nitroimidazole. On the other hand, because of the existence of impurity Ⅱ, the applicability of the current standard of related substance for ornidazole and sodium chloride injection was studied, and some optimization was made.The second part of this paper studied the related substances and stability of ornidazole and some related nitroimidazoles (metronidazole, tinidazole and secnidazole). And according to the actual process of manufacture and storage, structures of the impurities which were most likely to produce were analyzed. Experimental results showed that ornidazole and tinidazole decomposed under acidic, alkali and high temperature conditions, implying the pH value and sterilization process should be strictly controlled during the preparation of injection of these two drug substances. Metronidazole and secnidazole show good stability under the test. The third part studied the factors in relationship with the quality of nitroimidazoles Injections. Employing the amount of related substances and nitrite produced from the degradation of nitroimidazoles as the indicators, the influences of the pH value, sterilization process and the osomotic pressure regulators were tested. The results of this study show some reference value for the preparation of the injection of nitroimidazoles.