目的:建立人血浆中替诺福韦浓度的LC-MS/MS测定法,并用于富马酸替诺福韦二吡呋酯片的药动学和生物等效性研究.方法:采用自身双交叉试验设计,20例男性健康受试者随机分成2组,分别空腹口服受试制剂或参比制剂300 mg,0～72 h间隔采集血样.以LC-MS/MS法测定血浆替诺福韦浓度,DAS2.1.1计算药动学参数.结果:建立的LC-MS/MS法在2～1 200 ng· mL-1范围内线性关系良好,最低定量限为2 ng·mL-1,批内及批间精密度RSD均小于15％.受试制剂与参比制剂的Tmax均为(0.5±0.2)h,Cmax分别为(604±207)和(573±189) ng·mL-1,t1/2分别为(17.1±2.9)和(17.4±4.0)h,AUCo～72 h分别为(2 490±604)和(2 297±499)h·ng·mL-1.结论:建立的LC-MS/MS法准确可靠,富马酸替诺福韦二吡呋酯片两种制剂生物等效.%Objective: To establish a LC-MS/MS method for the determination of tenofovir in human plasma and study the pharmacokinetics and bioequivalence of tenofovir disoproxil fumarate tablets. Methods: In a randomized two-way crossover study, 20 healthy male volunteers were divided into two groups, and were administered respectively with a single oral dose of test and reference preparations containing 300 mg of tenofovir disoproxil fumarate after an over-night fast. The blood samples were collected at predetermined time intervals up to 72 hours. The plasma concentration of tenofovir was determined by LC-MS/MS. The pharmacokinetic parameters were estimated by DAS 2. 1. 1. Results:The established LC-MS/MS method had linear calibration range over 2～1 200 ng"mL-1 with a LLOQ of 2 ng o mL-1 for tenofovir in human plasma. The intra- and inter-batch standard deviations were less than 15% . The pharmacokinetic parameters for the test and reference tablets were as follows:Tmax both (0.5 ±0. 2) h, Cmax( 604 ±207) and (573 ±189) ng·mL-1 ,t1/2 ( 17. 1 ± 2. 9) and( 17. 4 ±4.0) h, AUC0～72h (2 490 ±604)and (2 297 ±499) h·ng·mL-1 , respectively. Conclusion: The method is suitable for the pharmacokinetic study of tenofovir disoproxil fumarate tablets. The two preparations are bioequivalent.rn[
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