HPLC-MS/MS法测定全血中西罗莫司的药物浓度

目的:建立简便、快速地测定人全血中西罗莫司血药浓度的HPLC-MS/MS方法。方法:全血样品经硫酸锌及含有子囊霉素(内标)的乙腈溶液沉淀后,取上清液20μL进样分析。采用Symmetry-C18色谱柱(2.1 mm×50 mm,3.5μm),流动相梯度洗脱,流速为0.5 mL.min-1,质谱采用电喷雾离子化电离源,经多反应监测模式检测。结果:西罗莫司和子囊霉素的保留时间分别为2.24 min和2.21 min,空白血浆中内源性物质不干扰测定;西罗莫司的血药浓度在1~30 ng.mL-1时,线性关系良好(r=0.999 5);日内、日间RSD值均小于10%,提取回收率为86.4%~90.4%。结论:本方法灵敏、准确、简单、快速,可用于西罗莫司的血药浓度监测和早期肝移植患者药代动力学研究。

Content determination of sirolimus in human whole blood by HPLC-MS/MS

Objective： To establish a simple and rapid HPLC-MS/MS method for determination of sirolimus in human whole blood. Methods： The samples of whole blood were deproteinated by zinc sulfate and internal standard reconstituted in acetonitrile and separated by a Symmetry-C18 column （2.1 mm × 50 mm, 3.5 μm） at the flow rate of 0.5 mL·min^-1 with gradient elution. Detection was performed on a tandem mass spectrometry with electrospray ionization source in positive ionmode. Multiple reactions monitoring mode was used to quantify sirolimus and internal standard respectively. Results： The retention time of sirolimus and intemal standard were 2.24 min and 2.21 min, respectively. The linear range of sirolimus was 1 - 30 ng-mL-1（ r = 0.999 5）. The intra-day and inter-day RSD were both less than 10%. The extraction recoveries were 86.4% - 90.4%. Conclusion： The method is sensitive, accurate, simple and rapid for monitoring of whole blood concentration of sirolimus and pharmacokinetic study in early liver tansplant recipients.