高效液相色谱-质谱法测定瑞舒伐他汀钙胶囊的药动学和生物等效性

Study of pharmacokinetics and bioequivalence of rosuvastatin capsules by high performance liquid chromatographic-mass spectrometry

目的:研究瑞舒伐他汀钙胶囊在健康人体内的药动学及其生物等效性。方法:20例健康受试者单剂量交叉口服10 mg瑞舒伐他汀供试制剂或参比制剂后,采用液相色谱-质谱法(LC-MS)测定人体血浆中不同时间点瑞舒伐他汀的浓度,计算其药动学参数和相对生物利用度,评价2制剂的生物等效性。结果:瑞舒伐他汀供试制剂和参比制剂主要药动学参数cmax分别为(12±4)和(11±4)μg·L-1,AUC0～72分别为(123±47)和(123±42)μg·h·L-1,tmax分别为(3．3±0．9)和(3．4±1．0)h,t1／2分另0为(18±7)和(18±5)h。本方法在0．1～20．0μg·L-1浓度范围内线性关系良好。最低可定量浓度为0．1μg·L-1, 2制剂主要药动学参数经统计学检验无显著差异。结论:本方法简单、快速、准确,很好的评价了2种制剂的生物等效。

AIM： To study the pharmaeokinetics and bioequivalence of rosuvastatin capsules in healthy people. METHODS： Twenty healthy male volunteers were enrolled into the single crossover study. A single dose of the suspension equivalent to rosuvastatin 10 mg or a reference preparation was given crossoverly to each of the individual, respectively. A sensitive and specific high performance liquid chromatography-mass spectrometric method （HPLC-MS） was used for the determination of rosuvastatin concentration in human plasma, and the bioequivalences of the suspension and the reference were evaluated by pharmacokinetic parameters and rela- tive bioavailability obtained. RESULTS： The pharmacokinetic parameters for rosuvastatin and reference preparationwere： Cmax （12±4） vs （11±4） μg·L^-1, AUC0-72 （123±47）vs （123±42） μg·L^-1, tmax （33＋0.9） vs （3.4 ± 1.0） h, t1/2 （18 ± 7） vs （18 ± 5） h, respectively, The linear correlative range was well within the concentration 0.1 - 20.0 μg·L^-1. The lowest detectable concentration of rosuvastatin was 0.1 μg·L^-1, with no significant difference in pharmacokinetic parameters. CONCLUSION： HPLC-MS merits for good sensitivity, accuracy, and simplicity, suitable for studing the pharmacokenitics and bioequivalent of rosuvastatin.