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目的:建立LC-MS方法测定盐酸曲美他嗪在健康人血浆中的浓度,并进行药物动力学研究和生物等效性评价。方法:18名男性健康受试者,随机分成2组,交叉口服受试制剂和参比制剂各20 mg,采用LC-MS法测定人血浆中曲美他嗪的浓度。结果:受试制剂与参比制剂的各主要药动学参数:t_(1/2)分别为(7.31±2.36)和(6.74±2.17)h,t_(max)分别为(2.1±0.9)和(1.8±0.6)h,C_(max)分别为(92.05±19.64)和(96.71±22.31)ng·ml~(-1),AUC_(0-24)分别为(691.24±171.82)和(706.31±189.60) ng·h·ml~(-1)。对两种制剂的参数C_(max)、AUC_(0-24)对数转换后先进行方差分析,再进行双单侧t检验。双单侧t检验结果表明上述两个参数生物等效,t_(max)经非参数法检验差异没有显著性意义(P>0.05),这表明两种制剂生物等效,相对生物利用度(101.5±26.7)%。结论:两种制剂具有生物等效。
OBJECTIVE: To establish a LC-MS method for the determination of trimetazidine hydrochloride in healthy human plasma and to evaluate its pharmacokinetics and bioequivalence. Methods: Eighteen male healthy subjects were randomly divided into two groups. Each of the 20 mg oral and 20 mg reference preparations was tested for the concentration of trimetazidine in human plasma by LC-MS. Results: The main pharmacokinetic parameters of test preparation and reference preparation were: t 1/2 (7.31 ± 2.36) and (6.74 ± 2.17) h, respectively, and t max were 2.1 ± 0.9 and (1.8 ± 0.6) h, and C max were (92.05 ± 19.64) and (96.71 ± 22.31) ng · ml -1, respectively, and the AUC 0-24 were 691.24 ± 171.82 and 706.31 ± 189.60) ng · h · ml -1. The variance of logarithm of C_ (max) and AUC_ (0-24) of the two preparations was analyzed before the double unilateral t-test. The results of two-sided t-test showed that the above two parameters were bioequivalent and there was no significant difference in t max between the two groups (P> 0.05), which indicated that the bioequivalence and relative bioavailability (101.5 ± 26.7)%. Conclusion: Both formulations are bioequivalent.