摘要
目的建立测定人血浆中奥美拉唑的HPLC—MS方法，并应用于药动学研究。方法血浆样品经蛋白沉淀法处理后，采用AlltimaC18色谱柱（2．1mm×100mm，3μm），以乙腈-0．05％甲酸溶液（50：50）为流动相，流速为0．2mL·min^-1，通过电喷雾电离源，以选择反应监测（SRM）方式进行正离子检测，通道分别为m／z346→198（奥美拉唑）和m／z324→127（内标，格列齐特），用非室模型计算药动学参数。结果奥美拉唑的线性范围为0．0025～2．0mg·L^-1，最低检测限为0．5μg·L^-1，日内、日间精密度均小于15％。低、中、高3个浓度提取回收率均大于95％，其主要药动学参数tmax为（2．5±0．7）h，ρmax为（1．3±0．3）mg·L^-1，AUC0-t为（2．8±1．2）mg·h·L^-1，t1/2为（1．1±0．3）h。结论该法操作简便，分析快速，灵敏度高，可用于人血浆中奥美拉唑的测定和药动学研究。
OBJECTIVE To develop a HPLC-MS method for the determination of omeprazole in human plasma and to investigate the pharmaeokinetics of omeprazole enteric-coated capsules. METHODS The plasma samples were simply pretreated by protein precipitation, and the plasma concentration of omeprazole was dertermined by HPLC-MS assay on an Alltima C18 column （2. l mm × 100 mm, 3 μm）. The mobile phase consisted of acetonitrile-0. 05% formic acid solution （50： 50） , at a flow rate of 0. 2 mL · min^-1. A Thermo Finnigan TSQ Quantum Discovery tandem mass spectrometer equipped with elecrtospray ionization source was used as detector and was operated in the positive ion mode. Selected reaction monitoring （SRM） using the precursor to product ion combinations of m/ z 346 to 198 and m/z 324 to 127 was performed to quantify omeprazole and the internal standard, respevtively. The pharmacokinetic parameters were calculated by non-compartment model statistics. RESULTS The linear calibration curves were obtained in the concentration range of 0. 002 5 - 2.0 mg · L^- 1. The lower limit of detection was 0. 5 μg · L^- 1 for omeprazole. The intra- and interday relative standard deviations （RSD） over the entire concentration range were less than 15%. The recoveries of three concentrations （0. 005 0, 0. 50 and 2.0 mg · L^-1 for omeprazole） ranged from 96. 1% to 98.6%. The pharmacokinetic parameters of omeprazole were as follows ： tmax （ 2. 5 ± 0. 7 ） h, ρmax （ 1. 3 ± 0. 3 ） mg · L ^-1, AUC0-t （ 2. 8 ± 1.2 ） mg · h · L ^-1 , t1/2 （ 1.1 ± 0. 3 ） h. CONCLUSION The method is convenient, rapid and sensitive. It can be used for the determination of omprazole in human plasma and pharmacokinetic investigation of omeprazole enteric-coated capsules.
出处
《中国药学杂志》
CAS
CSCD
北大核心
2010年第4期292-294,共3页
Chinese Pharmaceutical Journal
关键词
奥关拉唑
液相色谱-串联质谱法
血浆药物浓度
药动学
omeprazole
liquid chromatography-tandem mass spectrometry
plasma drug concentration
pharmacokinetics
作者简介
作者简介：楼永军，男，硕士，主管药师研究方向：药物的合成和质量控制Tel：（0571）86459413E—mail：louyongjun@hotmail．com
