LC-MS/MS法测定人血浆中替诺福韦质量浓度及其生物等效性研究  

LC-MS/MS Determination of Tenofovir in Human Plasma and Its Bioequivalence

作　　者：陈枳潓[1,2] 冯仕银 南峰[2] 余勤 梁茂植[2] 

机构地区：[1]四川大学华西药学院,成都610041 [2]四川大学华西医院国家药物临床试验机构.GCP中心,成都610041 [3]四川大学华西第二医院药物临床试验机构,成都610041

出　　处：《四川大学学报（医学版）》2018年第1期107-112,共6页Journal of Sichuan University(Medical Sciences)

摘　　要：目的建立液相色谱-串联质谱(LC-MS/MS)法测定人血浆中替诺福韦质量浓度,并应用于高脂餐后及空腹口服国产和进口替诺福韦二吡呋酯片的生物等效性研究。方法采用四周期随机交叉自身对照试验设计,24例健康男性受试者高脂餐后及空腹分别单剂量口服国产和进口替诺福韦二吡呋酯片300mg,LC-MS/MS法测定血浆中替诺福韦质量浓度,Winnonlin6.3软件计算主要药动学参数,并评价两种替诺福韦二吡呋酯片餐后及空腹服用的生物等效性。结果替诺福韦血浆标准曲线在3.13~500ng/mL范围内线性良好;批内、批间精密度相对标准偏差(RSD)均小于5.43%,回收率高且样品稳定性好。无论是高脂餐后给药还是空腹给药,药时曲线下面积AUC0-t、AUC0-∞和峰浓度(Cmax)的90%置信区间均在80.00%~125.00%范围内,达峰时间(Tmax)经非参数秩和检验,不同制剂间差异无统计学意义(P>0.05),两生物制剂等效。结论所建立的LC-MS/MS方法适用于人血浆中替诺福韦质量浓度的测定,国产替诺福韦二吡呋酯片与进口制剂生物等效。Objective To develop a liquid chromatography-tandem mass spectrometry （LC-MS/MS） method for detecting tenofovir in human plasma. Methods Twenty four healthy male volunteers received a single oral dose of 300 mg tenofovir disoproxil fumarate tablets under fasting and high-fat diet conditions in a randomized four-way crossover bioequivalence study with two preparations of tablets. Plasma samples were taken and analyzed using the LC-MS/MS method. The pharmacokinetic parameters of the two preparations were calculated and compared statistically to evaluate their bioequivalence using Phoenix Winnonlin6.3. Results Linear detection responses were obtained for tenofovir at the range from 3.13 to 500 ng/mL. The intra- and inter-day precisions were high, with lower than 5.43 % （relative standard deviation （RSD）%3, high recovery and good stability. The 90% confidence intervals of peak concentration （Cmax） of tenofovir and its area under the curve （AUC0-t and AUC0-∞ ） all fell within the bioequivalence limit 80.00 %-125.00 % under both fasting and high-fat diet conditions. No significant difference in peak time （Tmax） was demonstrated between the two preparations （P〉0.05）. Conclusion The LC-MS/MS method can be used for simultaneous determination of tenofovir in human plasma. The two preparations of tablets are bioequivalent.

关 键 词：替诺福韦 液相色谱-串联质谱 生物等效性 

分 类 号：O657.63[理学—分析化学] R969[理学—化学]