赖诺普利片在健康志愿者体内的生物等效性评价

目的:建立测定人血浆中赖诺普利浓度的液相色谱-串联质谱(LC-MS-MS)法,评价赖诺普利试验片与参比片的生物等效性。方法:20名志愿者随机单剂量双交叉口服赖诺普利试验片和参比片10 mg,采用沉淀蛋白法预处理血浆样品后,进行LC-MS-MS法测定。结果:试验片和参比片中药物主要药动学参数如下:cmax分别为(54±s 21)和(53±23)μg·L-1,tmax分别为(6．4±1．4)和(6．7±1．1)h,AUC0～36分别为(569±244)和(566±269)μg·h·L-1,AUC0～∞分别为(589±250)和(587±268)μg·h·L-1;按AUC0～36计算,赖诺普利试验片的相对生物利用度为(102±8)％。结论:本方法操作简单,灵敏度、准确度、精密度和定量分析线性关系均良好,符合生物样品测定要求;经统计学检验,试验片与参比片生物等效。

Bioequivalence assessment of two lisinopril tablets in healthy volunteers

AIM: To develop an analytical method based on LC-MS/MS for the quantification of lisinopril in human plasma and the assessment of bioequivalence for two kinds of lisinopril tablets in Chinese healthy male volunteers. METHODS: Plasma samples of 20 healthy male volunteers, who were administrated with a single oral dose of lisinopril test tablets (10 mg) and reference tablets (10 mg) according to a random 2-way crossover design, were prepared by a simple protein precipitation and then were determined by LC-MS/MS method. RESULTS: The main pharmacokinetic parameters of lisinopril test tablets and reference tablets were as follows: cmax(54±s 21) and (53±23)μg·L-1, tmax(6.4±1.4) and (6.7±1.1) h, AUC0-36(569±244) and (566±269)μg·h·L-1, AUC0-∞(589±250) and (587±268)μg·h·L-1, respectively. Calculating by AUC0-36, the relative bioavailability of lisinopril test tablets was (102±8) %. CONCLUSION: The analytical method based on LC-MS/MS for quantification and assessment of bioequivalence is simple, rapid and sensitive, proving the bioequivalence of lisinopril test tablets to the reference tablets.