LC-MS/MS法测定大鼠血中胆碱酯酶抑制剂XQ528及其代谢物美普他酚的浓度  

Determination of cholinesterase inhibitor XQ528 and its metabolite meptazinol in rat plasma by liquid chromatography-tandem mass spectrometry

作　　者：查媛[1,2] 谭波[3] 郑晓瑶 万旭[1,2] 邵夏炎[1,2] 杨萍[3] 张奇志[1,2] 

机构地区：[1]复旦大学药学院药剂学教研室,上海201203 [2]复旦大学药学院智能化递药教育部重点实验室,上海201203 [3]复旦大学药学院仪器测试中心,上海201203

出　　处：《中国临床药学杂志》2015年第2期89-94,共6页Chinese Journal of Clinical Pharmacy

基　　金：国家重大新药创制项目(编号2009ZX09301011-013)

摘　　要：目的建立测定大鼠血中胆碱酯酶抑制剂xQ528及其代谢物美普他酚浓度的高效液相一质谱联用法（LC．MS／MS）。方法血浆样品采用乙腈沉淀蛋白后进样测定，以尼泊金乙酯为内标。色谱柱：ZORBAX Eclipse XDBC，8（50mm×2．1mm，5μm），流动相：水（0．1％甲酸，A）～乙腈（0．1％甲酸，B），梯度洗脱，流速0．4mL·min^-1，柱温30℃，进样量20血，总分析时间为7min。质谱采用电喷雾离子源，以多反应离子监测模式进行定量分析。结果XQ528及其代谢物美普他酚的线性范围分别为0．05～50μg·L^-1和0．05—25μg·L^-1；批内RSD分别为3．1％和9．4％，批间RSD分别为7．4％和8．6％；提取回收率分别为102．1％-103．3％和104．2％-110．0％；基质效应均在85％～115％内。结论本方法灵敏度高、准确、快速，适于大鼠血浆中XQ528及其代谢物美普他酚浓度的测定和药动学研究。AIM To develop an LC-MS/MS method for determination of cholinesterase inhibitor XQ528 and its metabolite meptazinol in rat plasma. METHODS The analytes and the internal standard （IS, ethylparaben） were ex- tracted from 50 ttL aliquots of rat plasma by acetonitrile precipitation. Chromatographic separation was achieved by gradi- ent elution on a ZORBAX Eclipse XDB Cls column （50 mm×2.1 mm, 5μm） in a run time of 7 rain with the mobile phase consisted of water （0.1%formic acid, A） and acetonitrile （0.1%formic acid, B）, which was pumped at a flow rate of 0.4 mL·min^-1. The column temperature was set at 30 ℃ and the injection volume was 20μL. Detection of analytes and IS was done by tandem mass spectrometry, operated in positive ion and multiple reaction monitoring （MRM） mode. RESULTS The liner range of XQ528 and meptazinol in rats plasma were 0.05 - 50μg·L^-1 and 0.05 - 25μg·L^-1, respectively. The intra-batch RSD were less than 3.1% and 9.4% respectively,and the inter-batch RSD were less than 7.4% and 8.6% respectively. The extraction recoveries were 102.1% - 103.3 % and 104.2 % - 110.0%, respectively. The matrix effects were all within 85% - 115%. CONCLUSION The method is sensitive, accurate and fast, and suitable for the pharmacokinetic study of XQ528 formulation.

关 键 词：XQ528 美普他酚 高效液相-质谱联用 血浆 药动学 

分 类 号：R965[医药卫生—药理学] O657.63[医药卫生—药学]