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目的建立同时测定人血浆中兰索拉唑及其代谢产物5’-羟基兰索拉唑和兰索拉唑砜的LC-MS/MS法。方法血浆样本用乙腈沉淀蛋白后,选用Zorbax SB-C18 Narrow-Bore色谱柱(150 mm×2.1 mm,5μm),以甲醇︰10 mmol.L-1乙酸铵(65︰35,V/V)为流动相,流速为0.4 mL.min-1。选用API3200型三重四极杆串联质谱仪的多重反应监测(MRM)扫描方式进行监测,电喷雾离子化源,负离子方式。结果兰索拉唑、5’-羟基兰索拉唑、兰索拉唑砜以及内标奥美拉唑的保留时间分别为2.63、1.56、2.21、2.30 min;血浆中兰索拉唑、5’-羟基兰索拉唑、兰索拉唑砜的线性范围分别为2.00～800、1.00～400、0.200～80.0μg.L-1(r>0.99),定量下限分别为2.00、1.00、0.200μg.L-1;日内、日间相对标准差(RSD)均小于8.0%;相对偏差(RE)均在±6.0%的范围以内;提取回收率较高,且可重现;兰索拉唑、5’-羟基兰索拉唑、兰索拉唑砜在各种贮存条件下均较稳定。该方法成功地应用于兰索拉唑肠溶片在中国健康人体内的药动学研究,兰索拉唑、5’-羟基兰索拉唑、兰索拉唑砜的ρmax分别为165～1400、15.8～177、10.2～530μg.L-1,AUC0-t分别为651～7 189、99.3～639、20.5～4 372μg.h.L-1。兰索拉唑及其代谢产物的药动学存在显著的个体间差异。结论该方法快速、灵敏、专属性强、重现性好,适用于兰索拉唑及其代谢产物的人体药动学研究。
OBJECTIVE To establish a LC-MS / MS method for the simultaneous determination of lansoprazole and its metabolites 5’-hydroxy-lansoprazole and lansoprazole sulfone in human plasma. Methods The plasma samples were separated on a Zorbax SB-C18 Narrow-Bore column (150 mm × 2.1 mm, 5 μm) with methanol: 10 mmol·L-1 ammonium acetate (65:35, V / V) Mobile phase at a flow rate of 0.4 mL.min-1. The multi-reaction monitoring (MRM) scanning mode of API3200 triple quadrupole mass spectrometer was used for monitoring, electrospray ionization source and negative ion mode. Results The retention time of lansoprazole, 5’-hydroxy lansoprazole, lansoprazole sulfone and the internal standard omeprazole were 2.63,1.56,2.21,2.30 min, respectively. The plasma lansoprazole, 5 ’ The linear ranges of L-lansoprazole and lansoprazole sulfone were 2.00 ~ 800,1.00 ~ 400,0.200 ~ 80.0μg.L-1 (r> 0.99), the lower limits of quantitation were 2.00,1.00,0.200μg. L-1. The relative standard deviations (RSDs) were both less than 8.0% and the relative deviations (REs) were all within ± 6.0%. The recoveries were high and reproducible. Lansoprazole, 5 ’-hydroxyl-lansoprazole and lansoprazole sulfone are stable under various storage conditions. The method was successfully applied to the pharmacokinetics of lansoprazole enteric-coated tablets in healthy Chinese. The ρmax of lansoprazole, 5’-hydroxyl lansoprazole and lansoprazole sulfone were 165 ~ 1400 , 15.8 ~ 177,10.2 ~ 530μg.L-1, AUC0-t were 651 ~ 7 189,99.3 ~ 639,20.5 ~ 4 372μg.hL-1. There are significant inter-individual differences in the pharmacokinetics of lansoprazole and its metabolites. Conclusion The method is rapid, sensitive, specific and reproducible and is suitable for human pharmacokinetics of lansoprazole and its metabolites.