目的 建立人血浆中兰索拉唑的反相高效液相色谱紫外检测法,进行兰索拉唑的人体药动学研究。方法 血浆样品以乙醚提取,非那西丁为内标,采用Kromasil100-5 C8(4.6 mm×150 mm)色谱柱,以水-乙腈-二乙胺(用磷酸调pH 6.7)(600∶400∶1.2)溶液为流动相,流速0.8 mL·min-1,柱温40 ℃,检测波长285 nm。12名健康受试者,男女各半,采用随机开放自身对照三交叉,单剂量静脉滴注低(15 mg)或中 (30 mg) 或高 (60 mg) 剂量的注射用兰索拉唑,测定血浆中兰索拉唑浓度,计算兰索拉唑的人体药动学参数,并对其进行统计分析。结果 线性范围49.0~4 900.0 ng·mL-1,最低定量限为49.0 ng·mL-1(S/N > 10),方法学回收率为93.3%~100.1%,提取回收率大于82%。15 mg剂量组主要药动学参数:ρmax为(1 105.65±506.24)ng·mL-1,tmax 为(0.24±0.14)h,t1/2为(3.01±1.77)h, MRT0-12为(0.93±0.95)h,AUC0-12为(991.16±814.49)ng·h ·mL-1;30 mg剂量组,ρmax为(2 171.33±799.02)ng·mL-1,tmax 为(0.51±0.16)h,t1/2为(3.98±2.51 )h, MRT0-12为(1.91±0.83)h,AUC0-12为(3 495.87±1 770.92)ng·h ·mL-1; 60 mg剂量组,ρmax为(4 070.53±643.04)ng·mL-1,tmax 为(1.02±0.07)h,t1/2为(3.73±1.55)h,MRT0-12为(2.42±0.65)h,AUC0-12为(8 351.14±2 599.90)ng·h ·mL-1。结论 本法简便、灵敏、重现性好。健康受试者静脉滴注15、30、60 mg兰索拉唑后,其体内药动学过程基本上呈现线性动力学特征而无饱和性,血浆药物浓度-时间曲线符合二室模型。
Abstract
OBJECTIVE To establish a HPLC method for the determination of lansoprazole in human plasma and determine the pharmacokinetics of lansoprazole. METHODS Lansoprazole and internal standard phenacetin were extracted from plasma with ether. The content of lansoprazole was detected by ultraviolet detector at 285 nm with Kromasil100-5 C8(4.6 mm×150 mm) column. The mobile phase consisted of water-acetonitrile-diethylamine (adjusted to pH 6.7 with H3PO4) (600∶400∶1.2)at a flow rate of 0.8 mL·min-1.The column temperature was 40 ℃. A single-dose, open-label, randomized, three-period crossover dose study was carried out in 12 healthy volunteers. The subjects received intravenous infusion of 15, 30 and 60 mg lansoprazole. The concentrations of lansoprazole in plasma were determined by HPLC method and the pharmacokinetic parameters were calculated.RESULTS The linear range was 49.0 to 4 900.0 ng·mL-1(r=0.999 9). The lowest quantitive concentration was 49.0 ng mL-1(S/N > 10).The average method recovery was 93.3% to 100.1%, and extracted recovery was over 82% for the low, middle, high control samples. The main pharmacokinetic parameters of the three groups(15,30 and 60 mg) were as follows:ρmax (1 105.65±506.24), (2 171.33±799.02) and (4 070.53±643.04) ng·mL-1,tmax (0.24±0.14), (0.51±0.16) and (1.02±0.07)h,t1/2(3.01±1.77), (3.98±2.51) and (3.73±1.55)h, MRT0-12(0.93±0.95), (1.91±0.83) and (2.42±0.65)h, AUC0-12 (991.16±814.49), (3 495.87±1 770.92), (8 351.14±2 599.90) ng·h ·mL-1. CONCLUSION This method is convenient, sensitive and reproducible, suitable for the determination of lansoprazole in human plasma for pharmacokinetics. Within the lansoprazole administration limit of 15-60 mg, the linear character of pharmacokinetics is showed in the body, which conforms to the two compartment models.
关键词
兰索拉唑 /
反相高效液相色谱法
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Key words
lansoprazole /
RP-HPLC /
plasma concentration /
pharmacokinetics
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参考文献
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脚注
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