Jian Wang, Jinjin Zhou, Yu Xu
Sep 15, 2019
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Influential Citations
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Journal
Rapid communications in mass spectrometry : RCM
Abstract
RATIONALE Eleven impurities and one polymerized impurity in mezlocillin were identified and their forming mechanisms were investigated in this study. The sources and arising reasons of impurities were revealed, which may guide industry to improve the manufacturing process and storage conditions and reduce impurity content in products. The result from this study also provided scientific basis for the improvement of official monographs inpharmacopoeias. METHODS The impurity profiles and polymerized impurity in mezlocillin were studied by the multiple heart-cutting two-dimensional liquid chromatography coupled with ion trap/time-of-flight mass spectrometry (2D LC-IT-TOF MS) with both positive and negative modes of electrospray ionization. Target eluents from the first dimensional chromatography with non-volatile mobile phase were trapped and sent to the second dimensional chromatography with volatile mobile phase by a switching valve. The structures of the impurities in mezlocillin drug substance were deduced based on the high-resolution MSn data. RESULTS In the environment of water, oxygen, high temperature, acid and base, a series of degradation products could be easily produced from mezlocillin. Mezlocillin was hydrolyzed into impurity I, impurity IV, impurity V and impurity X, and was degraded into impurity III by methanolysis. Mezlocillin was oxidized into sulfoxide by producing impurity XI. Furthermore, impurity VI, impurity VII, impurity VII and impurity IX were all isomers of mezlocillin. The proposed forming pathways of these products were demonstrated in this study. CONCLUSIONS Eleven degradation impurities and one polymerized impurity in mezlocillin were separated and characterized. Based on characterization of impurities, this study found out the mechanism of impurity production and provided guidance for manufacturer to improve the process and storage condition and reduce impurity content.