HPLC-MS／MS法测定大鼠血浆中兰索拉唑及其代谢产物的浓度

目的：建立大鼠血浆中兰索拉唑及其代谢产物5-羟基兰索拉唑、兰索拉唑砜的HPLC-MS／MS测定方法。方法：色谱条件：色谱柱：Diamonsil C18柱（150mm×2．1mm，5um）；流动相：乙腈-水（合0．01％甲酸及2mmol·L-1的醋酸铵（43：57，V／V）；流速：0．3ml·min-1；柱温：40℃；进样量10ul。质谱条件：电喷雾离子源（ESI），以多反应监测离子方式测定兰索拉唑及其代谢产物，选择性监测质荷比（m／z）为368．0／163．9（兰索拉唑），384．1／179．9（5-羟基兰索拉唑），383．9／115．9（兰索拉唑砜），326．0／280．1（内标奥美拉唑）。样品用乙腈沉淀蛋白处理。结果：兰索拉唑、5-羟基兰索拉唑、兰索拉唑砜的线性范围分别为11．40～4560．00，1．26～504．00，1．24～496．00ng·ml-1；定量下限分别为11．40，1．26，1．24ng·ml-1；批内、批间精密度RSD均〈15％。结论：该方法灵敏、准确、快速、专属性好，适用于兰索拉唑及其代谢产物在大鼠体内的药代动力学研究。

Determination of Lansoprazole and its Metabolites in Rat Plasma by HPLC-MS/MS

Objective： To establish a liquid chromatography-mass spectrometry （LC-MS/MS） -based method for determining lansoprazole and its metabolites 5-hydroxy lansoprazole and lansoprazole sulphone in rat plasma. Method： The determination was performed under the following LC and MS conditions ： LC ： Diamonsil Cls column （ 150 mm × 2. 1 mm ,5 um） ; the mobile phase consisted of acetonitrile-2 mmol.L-1 ammonum acetate solution including 0.01% formic acid （43：57 ,V/V） ;the flow rate was 0. 3 ml.min-1 ;column temperature was 40 ℃. MS ：electrospray ionization source in the triple quadruple tandem mass spectrometer （ESI） ,and the selected ion mass monitoring （m/z） 368.0/163.9 for lansoprazole,384. 1/179.9 for 5-hydroxy lansoprazole,383.9/115.9 for lansoprazole sulphone and 326.0/280.1 for the internal standard omeprazole. The plasma was pretreated with acetonitrile. Result： The linear range of lansoprazole,5-hydroxy lansoprazole and lansoprazole sulphone in rat plasma was 11.40-4560. 00, 1.26-504. 00 and 1.24-496.00 ng. ml - 1, respectively. The lower quantitative limit was 11.4,1.26 and 1.24 ng. ml - 1, respectively, with intra-day and inter-day precision RSD below 15%. Conclusion： The method is sensitive, accurate,specific and well applicable in pharmacokinetic study on lansoprazole and its metabolites in rat.