论文部分内容阅读
目的:建立人体血浆中辛伐他汀的LC/MS/MS测定方法,并研究辛伐他汀片在男性健康志愿者体内的药物动力学行为,评价其生物利用度和生物等效性。方法:采用两制剂双周期自身对照试验设计。18名男性健康志愿者随机交叉服用单剂量辛伐他汀试验片剂和参比片剂20mg,采用液相色谱-串联质谱(LC/MS/MS)分析方法测定血浆辛伐他汀的浓度。采用DAS2.0程序计算药物动力学参数和相对生物利用度,并进行等效性评价。结果:测定单剂量口服20mg辛伐他汀参比片剂和试验片剂的AUC_((0→24))分别为(14.90±5.86)和(14.37±4.94)ng·h·ml~(-1),AUC_((0→∞))分别为(15.62±6.29)和(14.78±5.02 )ng·h·ml~(-1);C_(max)分别为(4.54±2.11)和(4.00±1.34)ng·ml~(-1);T_(max)分别为(1.75±0.79)和(1.39±0.65)h。以AUC_((0→24))与AUC_((0→∞))计算相对生物利用度分别为(108.0±52.7)%和(106.4±52.5)%。结论:该法准确灵敏,测得的数据可靠,统计分析表明两种制剂生物等效。
OBJECTIVE: To establish a method for the determination of simvastatin in human plasma by HPLC / MS / MS. The pharmacokinetics of simvastatin tablet in male volunteers was evaluated and its bioavailability and bioequivalence were evaluated. Methods: Two-cycle self-controlled trial design was used. Twenty-eight male healthy volunteers were randomized to receive single-dose simvastatin test tablets and reference tablets 20 mg and plasma concentrations of simvastatin were determined by liquid chromatography-tandem mass spectrometry (LC / MS / MS). The DAS 2.0 program was used to calculate pharmacokinetic parameters and relative bioavailability and to evaluate equivalence. Results: The AUC_ ((0 → 24)) of the 20 mg simvastatin reference tablets and the test tablets were (14.90 ± 5.86) and (14.37 ± 4.94) ng · h · ml -1, respectively, , (15.62 ± 6.29) and (14.78 ± 5.02) ng · h · ml -1, respectively, and the C max values were (4.54 ± 2.11) and (4.00 ± 1.34) ng · ml -1 and T max were (1.75 ± 0.79) and (1.39 ± 0.65) h, respectively. The relative bioavailability calculated with AUC _ ((0 → 24)) and AUC _ ((0 → ∞)) was (108.0 ± 52.7)% and (106.4 ± 52.5)%, respectively. Conclusion: This method is accurate and sensitive, the measured data is reliable, and statistical analysis shows that the two preparations are bioequivalent.