摘要
目的建立测定大鼠血浆中兰索拉唑的HPLC法,并比较兰索拉唑分别与铝碳酸镁、莫沙比利联合用药的大鼠体内药动学行为。方法18只健康雄性Wistar大鼠随机分为兰索拉唑组、兰索拉唑联合铝碳酸镁组和兰索拉唑联合莫沙比利组,灌胃给药。大鼠血浆样品经甲醇沉淀蛋白处理后进行药物浓度的测定。色谱柱为ODS-C18柱(150mm×4.6mm,5μm);流动相:甲醇水(53:47);检测波长:285nm。结果兰索拉唑在50~5000ng·mL^-1线性关系良好,方法回收率为84.0%~90.8%。3种给药方式兰索拉唑的主要药动学参数分别为:tmax:(0.28±0.04)、(2.17±0.26)和(0.28±0.12)h;Cmax:(1939±473.2)、(953±261.0)和(1889±721.9)ng·mL^-1;t1/2:(1.52±0.55)、(1.45±0.40)和(1.67±0.22)h;AUC0-10:(2559±519.5)、(3318±1082)和(3238±1514)ng·h·mL^-1;AUC0-∞:(2729±598.6)、(3498±1149)和(3438±1568)ng·h·mL^-1。经独立样本t检验及非参数检验分析,联用后,铝碳酸镁能明显推迟兰索拉唑达峰时间并降低峰浓度;莫沙比利对兰索拉唑的药动学行为没有显著影响。结论本方法专属性强、准确、简便,可为临床合理用药提供依据。
Objective To establish an HPLC method for comparative study on pharmacokinetics of lansoprazole in combination with hydrotalcite or mosapride in rat plasma. Methods Eighteen Wistar rats were randomly divided into 3 groups for oral administration, respectively. The plasma samples were taken by protein preciptation with methanol and separated on an ODS C18 (150 mm×4.6 mm, 5μm) column with methanol-water (53 : 47) as the mobile phase. The detective wavelength was 285 nm. Results The calibration curve was linear within 50-5 000 ng·mL^-1 , and the method recovery was within 84.0%-90.8%. The main pharmacokinetic parameters of lansoprazole in the 3 groups were: tmax(0.28 ± 0.04), (2.17 ± 0.26), and (0.28 ± 0.12) h; Cmax (1 939 ± 473.2), (953±261.0), and (1 889 ± 721.9) ng·mL^-1 t1/2 (1.52 ± 0.55), (1.45 ± 0.40), and (1.67 ± 0.22) h; AUC0-10 (2 559 ± 519.5), (3 318 ± 1082) and (3 238 ± 1 514) ng·h·mL^-1; andAUC0-∞ (2 729±598.6), (3 498± 1 149), and (3 438 ± 1 568) ng ·h·mL^-1, respectively. According to independent-sample t test and nonparametric tests, t of lansoprazole was significantly extended, and Cmax was decreased by the co-administration of hydrotalcite; while the pbarmacokinetic parameters of lansoprazole were not affected by the co-administration of mosapride. Conclusion This method is specific, accurate and simple, and can provide reference for the rational use of medicine.
出处
《中南药学》
CAS
2009年第5期349-352,共4页
Central South Pharmacy