LC-MS/MS法同时测定人血浆中兰索拉唑与代谢产物的浓度及其药动学研究(英文)

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。

LC-MS/MS method for simultaneous quantitation of lansoprazole and its metabolites in human plasma and application to a pharmacokinetic study

AIM To develop a rapid and sensitive liquid chromatography-tandem mass spectrometric(LC-MS/MS)method for the simultaneous quantitation of lansoprazole and its metabolites 5’-hydroxy lansoprazole and lansoprazole sulphone in human plasma.METHODS After a simple protein precipitation using acetonitrile,the analytes and internal standard(IS),omeprazole,were separated on a Zorbax SB-C18 Narrow-Bore column using methanol-10 mmol·L-1 ammonium acetate(65 ∶ 35,V/V)as mobile phase at a flow rate of 0.4 mL·min-1.Detection was by electrospray negative ionization mass spectrometry using multiple reaction monitoring(MRM)mode.RESULTS Lansoprazole,5’-hydroxy lansoprazole,lansoprazole sulphone and IS were eluted at 2.63,1.56,2.21,and 2.30 min,respectively.The method was linear in the concentration ranges of 2.00-800 μg·L-1 for lansoprazole,1.00-400 μg·L-1 for 5’-hydroxy lansoprazole and 0.200-80.0 μg·L-1 for lansoprazole sulphone,with intra- and inter-day precision as relative standard deviation(RSD)< 8.0% and accuracy as relative error(RE)within ± 6.0%.The extraction recoveries were high and reproducible.Lansoprazole,5’-hydroxy lansoprazole,and lansoprazole sulphone were found to be stable under various storage conditions.The method was successfully applied to a pharmacokinetic study in healthy Chinese volunteers after a single oral dose of lansoprazole enteric-coated tablets,in which the ρmax values were 165-1 400,15.8-177,and 10.2-530 μg·L-1,and the AUC0-t values were 651-7189,99.3-639,and 20.5-4 372 μg·h·L-1 for lansoprazole,5’-hydroxy lansoprazole,and lansoprazole sulphone,respectively.There was significant inter-individual difference in the pharmacokinetics of lansoprazole and its metabolites.CONCLUSION The established method is rapid,sensitive,selective,reliable and sufficient for pharmacokinetic study of lansoprazole and its metabolites.