摘要
目的 建立人血浆中雷贝拉唑钠的HPLC-MS测定方法，测定健康志愿者口服雷贝拉唑钠肠溶片后的血药经时过程，并对受试制剂和参比制剂的生物等效性进行评价。方法20名男性健康受试者随机交叉两种雷贝拉唑钠肠溶片20mg后，采用HPLC-MS分析测定人血浆中雷贝拉唑钠的浓度，评价两种雷贝拉唑钠肠溶片的生物等效性。HPLC-MS的色谱柱为C18柱，流动相为10mmol·L^-1的醋酸铵水溶液（舍0．3％甲酸）-甲醇（25：75，v／v），流速为1．0mL·mln^-1。检测离子为雷贝拉唑的[M＋H]＋离子m／z360．1和兰索拉唑（内标）的[M＋H]＋离子m／z370．0，裂解电压为100V。结果在0．5～1200ng·mL^-1范围内雷贝拉唑钠线性良好（r=0．9995），最低定量限为0．5ng·mL^-1，批内、批间精密度均小于8.0％。以AUC0-12州计算，受试制剂的相对生物利用度为99．2±11．8％。结论本试验建立的测定方法灵敏、准确、简便．适用于雷贝拉唑钠血药浓度的测定及药代动力学研究。
OBJECTIVE To develop an HPLC-MS method for the determination of rabeprazole in human plasma and to evaluate the pharmacokinetics and bioequivalence of two rabeprazole enteric-coated tablets in human. METHODS A randomized two way crossover design was conducted in 20 volunteers. Each volunteer was randomized to receive two kinds of rabeprazole enteric-coated tablets. The rabeprazole plasma concentration was determined by the HPLC-MS method, and the bioequivalence of two rabeprazole enteric-coated tablets in human was evaluated. HPLC-MS was performed on a C18 column with a mobile phase of 10 mM ammonium acetate solution containing 0. 3% formic acid - methanol （25： 75, v/v） at a flow rate of 1 mL·min^-1 HPLC-MS was performed in the selected ion monitoring （SIM） mode using target ions[M ＋ H] ＋ m/z 360. 1 for rabeprazole and [ M ＋ H]＋ m/z 370. 0 for lansoprazole （the internal standard） with the fragment voltage of 100 V. RESULTS The method was linear over the concentration range of 0. 5 - 1200 ng·mL^-1. The lower limit of quantification （LLOQ） was 0. 5 ng· mL^-1. The intra- and inter-run precisions were both less than 8 %. The relative bioavailability of test rabeprazole enteric-coated tablets was 99.2±11.8%. CONCLUSION The assay was simple, accurate, and suitable for the pharmacokinetics study of rabeprazole in human plasma.
出处
《海峡药学》
2007年第6期96-99,共4页
Strait Pharmaceutical Journal
