液相色谱-质谱联用分析紫杉醇和多西他赛中流动相体系的优化

 目的 分别通过质谱的两种进样方式——直接进样和色谱进样,考察并比较两种进样方式、不同添加剂条件下紫杉醇和多西他赛的离子化规律。方法 将含有不同添加剂的紫杉醇和多西他赛混合溶液分别通过针泵或液相系统导入电喷雾电离源进行质谱检测,获取待测化合物的质谱图或色谱图。研究溶液或流动相中添加剂的种类、浓度、pH值对紫杉醇和多西他赛离子化效率的影响。结果 两种进样方式所呈现的待测化合物质谱响应的变化情况一致,均以1 mmol/L甲酸铵溶液(pH 6.5)为添加剂所展现的离子化效率最高、响应强度最大。结论 在建立紫杉醇或多西他赛的液相色谱 质谱联用(LC-MS/MS)定量方法时,采用质谱直接进样方式对流动相中的水相组成进行优化的方法是高效、便捷和可靠的。在此基础上建立的人血浆中紫杉醇浓度的LC-MS/MS分析方法,经方法学验证表明灵敏度高、结果重现性好。

Optimization of mobile phase composition in development of an LC-MS/MS method for quantitation of paclitaxel and docetaxel

Objective To investigate and compare the ionization behaviors of paclitaxel and docetaxel by exposing to various additives in two sampling ways:direct infusion or by liquid chromatograph into mass spectrometer.Methods The working solutions of paclitaxel and docetaxel,mixed with different additives,were led into the electrospray ionization source,via a syringe pump or via the liquid chromatographic system,for detection and collection of mass spectra or chromatograms of the analytes.The influence of additives,with various sorts,concentrations and pH,in solutions or mobile phases on the ionization efficiency of paclitaxel and docetaxel were studied.Results Similar patterns of mass spectra intensity variations were observed between these two sampling methods,in that the highest ionization efficiency and strongest signal intensity were obtained when the analytes were exposed to the additive as 1 mmol/L ammonium formate (pH=6.5) in both methods.Conclusions Direct infusion of samples into mass spectrometer is an efficient,simple and reliable way to optimize the mobile phase composition in the development of liquid chromatography tandem mass spectrometry (LC-MS/MS) method for quantitation of paclitaxel and docetaxel.Based on these observations,a sensitive and reproducible LC-MS/MS method for the determination of paclitaxel in human plasma was successfully established and validated.