摘要
目的:建立快速、灵敏的高效液相色谱-串联质谱(HPLC-MS/MS)方法同时测定人血浆中替诺福韦艾拉酚胺(TAF)及其活性代谢产物替诺福韦(TFV)的浓度,并研究该药物在人体内的药动学特征。方法:采用Capcell pake ADME色谱柱(75 mm×2.1 mm,5μm),以0.1%甲酸水溶液-甲醇为流动相,梯度洗脱,流速0.4mL·min^-1,进样量5μL;采用多反应监测(MRM),选择质荷比(m/z)477.3/346.1(TAF)、288.2/176.0(TFV)、484.3/346.1(内标1:TAF-d7)及294.2/182.0(内标2:TFV-d6)进行检测。结果:TAF与TFV质量浓度分别在0.1~400 ng·mL^-1及0.4~20 ng·mL^-1范围内线性关系良好,定量下限分别为0.100 0ng·mL^-1及0.400 0 ng·mL^-1,日内、日间精密度均小于9.0%,准确度分别为94.1%~99.2%和95.5%~112.8%。健康中国人服用富马酸替诺福韦艾拉酚胺片25 mg后,TAF主要药动学参数:Cmax=(207.97±61.08)ng·mL^-1,T1/2=(0.54±0.15)h,AUC0-∞=(126.07±42.67)h·ng·mL^-1;TFV主要药动学参数:Cmax=(8.76±1.46)ng·mL^-1,T1/2=(29.47±4.16)h,AUC0-∞=(193.19±45.75)h·ng·mL^-1。结论:该方法适用于TAF及其代谢产物TFV的血药浓度检测,并提供药动学参数。
Objective:To develop a selective and rapid HPLC-MS/MS method for simultaneously determination of tenofovir alafenamide(TAF)and its active metabolite,tenofovir(TFV),in human plasma,in order to study the pharmacokinetics in healthy volunteers.Methods:The fractionation of the plasma sample and determination of TAF/TFV was achieved using HPLC-MS/MS equipped with Capcell pake ADME column(75 mm x 2.1 mm,5μm),using 0.1%formic acid water solution and methanol as mobile phase,respectively,by a gradient elution at 0.4 mL·min^-1 flow rate.The mass was captured by multiple reactions monitoring(MRM),with m/z of 477.3/346.1(TAF),288.2/176.0(TFV),484.3/346.1(internal standard 1:TAF-d7)and 294.2/182.0(internal standard 2:TFV-d,)as the characteristic ion masses.Results:Under the concentration range 0.1-400 ng·mL^-1 for TAF and 0.4-20 ng·mL^-1 for TFV,good linearity was achieved with0.100 0ng·mL^-1 and 0.400 0 ng·mL^-1 as lower limit of quantification,respectively.Both inter-and intraday precisions were bellow 9.0%and the accuracy was between 94.1%-99.2%for TAF and 95.5%^(-1)12.8%for TFV.The main pharmacokinetic parameters of TAF and TFV measured in healthy Chinese volunteers after oral administration TAF 25 mg were as follows:C_(max)=(207.97±61.08)ng·mL^-1,(8.76±1.46)ng·mL^-1;T1/2=(0.54±0.15)h,(29.47±4.16)h;AUC_(0-∞)=(126.07±42.67 hng·mL^-1,(193.19±45.75)h·ng·mL^-1.Conclusion:The HPLC-MS/MS method is validated for application in quantification of TAF and its metabolite TFV,and proved adaptable for following pharmacokinetic studies.
作者
胡伟
杨乐婷
蒋学华
王凌
HU Wei;YANG Le-ting;JIANG Xue-hua;WANG Ling(West China School of Pharmacy,Sichuan University,Chengdu 610041,China;Chengdu Finelyse Pharmaceutical Technology Co.,Ltd.,Chengdu 610031,China)
出处
《药物分析杂志》
CAS
CSCD
北大核心
2019年第7期1200-1206,共7页
Chinese Journal of Pharmaceutical Analysis
作者简介
通信作者: 王凌,Tel :( 028 ) 85501370;E-mail: rebeccawang312@gmail.com 第一作者:胡伟, Tel:( 028 ) 85501370;E-mail: sandyhwx@ 163.com
