The Analysis Of Influence Factors Of Quinolones By Liquid Chromatography-mass Spectrometry

Quinolones were widely used in clinical treatment of various infectious diseasescaused by bacteria, thus it is of great importance to control the quality of the drugs toensure the safety and efficacy. There were varieties of external environment factorscausing the degradation or deterioration of them, which brings the need for reliable, fastand low-cost analysis of this class of compounds and their degradation.With continuous development of the high resolution mass spectrometer, liquidchromatography-mass spectrometry shows a unique advantage in the study ofcompounds’ structures and stability, which can deduce the structures of targetedcompounds by obtaining accurate molecular weight and characteristic fragmenatinformation. It has became an important method in structural analysis of unknowncompounds in a complex matrix and quality control of drugs.In this paper, five represpctative quinolones were investigated by ESI-MS/MS andthe characteristic product ions were obtained. Major fragmentation pathways were thelosses of some small neutral molecules, such as H2O, CO2, HF, CO, CH2CH2and cyclopropene, and four-membered H rearrangement in piperazine moiety. Six kindsof quinolone bulk drugs treated with high humidity, high temperature, photolysis, strongacid, strong alkali, H2O2in10days were analysed by liquid chromatography-massspectrometry (LC-MS). Possible degradation mechanisms were proposed and structuresof their degradation products were determined by tandem mass spectrometry. Thestability and influence factors of the six quinolones under these conditions wereclarified. It was found that temperature, humidity and oxidation have a remarkablyinfluence on the stability of quinolones. Under high temperature, norfloxacin,ciprofloxacin hydrochloride and sarafloxacin hydrochloride produce many degradationproducts; Under the light, levofloxacin hydrochloride produces five obviousdegradation products; All the quinolones except for ciprofloxacin hydrochloride areprone to oxidation by H2O2, and enrofloxacin produces most of degradation products;for these compounds, only levofloxacin hydrochloride and sarafloxacin hydrochloridedegradate in alkaline conditions, and corresponding degradation products were detectedat m/z336and751, respectively. High humidity and strong acid have no obviouslyinfluence on the six quinolnes.By investigating the degradation products under high humidity, high temperature, photolysis, oxidation, strong acid and strong alkali on the six quinolones, their stabilitycan be comprehensively understand. This study provide scientific theories ondeterminating the formulation, process design and product storage condition for thedrugs.