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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Kromasil(100-5 C8(4.6 mm×150 mm)色谱柱,以水-乙腈-二乙胺(用磷酸调pH6.7)(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。
Objective To establish a reverse-phase high-performance liquid chromatography (UV) detection method of lansoprazole in human plasma and study the pharmacokinetics of lansoprazole. Methods Plasma samples were extracted with ether and phenacetin was used as internal standard. The samples were separated on a Kromasil (100-5 C8 (4.6 mm × 150 mm) column with water-acetonitrile-diethylamine (pH6.7 with phosphoric acid) (600 : 400: 1.2) as the mobile phase, the flow rate was 0.8 mL.min-1, the column temperature was 40 ℃ and the detection wavelength was set at 285 nm.12 Healthy subjects were divided into two groups: male and female, Lansoprazole was injected intravenously at low (15 mg) or medium (30 mg) or high (60 mg) doses, and lansoprazole concentrations in plasma were measured to determine the human pharmacokinetic parameters of lansoprazole The results showed that the linear range was 49.0-4 900.0 ng.mL-1, the lowest limit of quantification was 49.0 ng.mL-1 (S / N> 10), and the recovery rate was 93.3% -100.1% The main pharmacokinetic parameters of 15 mg dose group were ρmax of (105.65 ± 506.24) ng.mL-1, tmax of (0.24 ± 0.14) h and t1 / 2 of (3.01 ± 1.77) h and MRT0 -12 was (0.93 ± 0.95) h, and AUC0-12 was (991.16 ± 814.49) ng.h.mL-1; in the 30 mg dose group, ρmax was (2 171.33 ± 799.02) ng.mL- ± 0.16) h, t1 / 2 was (3.98 ± 2.51) h, MRT0-12 was (1.91 ± 0.83) h, AUC0-12 was (3 495.87 ± 1 770.92) ng.h.mL- , ρmax is (4 070.53 ± 643.04 ng.mL-1, tmax was (1.02 ± 0.07) h, t 1/2 was (3.73 ± 1.55) h, MRT0-12 was (2.42 ± 0.65) h and AUC0-12 was (8 351.14 ± 2 599.90) ng.h.mL-1 .Conclusion This method is simple, sensitive and reproducible.After intravenous infusion of 15, 30 and 60 mg of lansoprazole in healthy subjects, the pharmacokinetics in vivo are basically the same Linear kinetic characteristics without saturation, plasma drug concentration - time curve in line with the two-compartment model.