Simultaneous analysis of antiretroviral drugs abacavir and tenofovir in human hair by liquid chromatography-tandem mass spectrometry
Simultaneous analysis of antiretroviral drugs abacavir and tenofovir in human hair by liquid chromatography-tandem mass spectrometry
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DOI：
10.1016/j.jpba.2012.10.023
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发表时间：
2013-02-23
影响因子：
3.4
通讯作者：
Naughton, Declan P.
中科院分区：
文献类型：
--
作者：
Shah, Syeda A. B.;Mullin, Rebecca;Naughton, Declan P.
建立了一种灵敏度高、重复性好的同时定量头发中抗逆转录病毒药物阿巴卡韦和替诺福韦的LC-MS/MS方法。根据美国食品和药物管理局（FDA）的指导方针对该方法的参数进行了验证：特异性、稳定性、检出限（LOD）、定量限（LOQ）、线性、准确度、精密度和回收率。头发样品（50 mg）被净化并进行甲醇提取，其中加入1ml甲醇和内标abacvir -d4，最终浓度为0.15 ng/mg头发。16 h后，用乙酸铵缓冲液和甲基叔丁基醚与乙酸乙酯（1:1）的混合物液液萃取回收药物。样品在注射前用200 μ l乙腈：水（1:1）复配，进行LC-MS/MS。两种药物的LOD和LOQ值分别为0.06和0.12 ng/mg（药/发）。两种药物在药/毛浓度0.12 ~ 4.0 ng/mg范围内线性良好，回归系数（r(2)）均为0.999。准确度、精密度和回收率均在FDA规定范围内。头发样品中替诺福韦和阿巴卡韦的药物浓度分别为0.12 ~ 4.48 ng/mg和0.32 ~ 1.67 ng/mg。这是首个同时测定头发中这两种关键抗逆转录病毒药物的方法的完整报告。新开发的方法有助于今后对人类头发中的替诺福韦和阿巴卡韦进行常规分析，并可用于治疗药物监测和药物依从性研究，有助于制定联合抗逆转录病毒治疗方案的治疗变化决策。(C) 2012 Elsevier B.V.版权所有
A sensitive and reproducible method has been developed and validated for the simultaneous quantification of the key antiretroviral drugs abacavir and tenofovir in hair using LC-MS/MS. The method was validated according to the US Food and Drug Administration (FDA) guidelines for the parameters: specificity, stability, limits of detection (LOD), limits of quantification (LOQ), linearity, accuracy, precision and recovery. Hair samples (50 mg) were decontaminated and subjected to methanolic extraction, where 1 ml methanol was added along with the internal standard abacavir-d4 at a final concentration of 0.15 ng/mg hair. After 16 h, the drugs were recovered by liquid-liquid extraction using ammonium acetate buffer and a mixture of methyl tert-butyl ether: ethyl acetate (1:1). The samples were reconstituted with 200 mu l acetonitrile:water (1:1) prior to injection for LC-MS/MS. The LOD and LOQ values were 0.06 and 0.12 ng/mg (drug/hair) for both drugs. Calibration curves were linear in the concentration range of 0.12-4.0 ng/mg of drug/hair with regression coefficient (r(2)) value of 0.999 for both drugs. The data for accuracy, precision and recovery were within the FDA limits. The concentrations of the drugs in the hair samples ranged from 0.12 ng/mg to 4.48 ng/mg and 0.32 ng/mg to 1.67 ng/mg for tenofovir and abacavir, respectively. This is the first full report of a method for the simultaneous determination of these two key antiretroviral drugs in hair. The newly developed method is useful for future routine analysis of tenofovir and abacavir in human hair and could be used in therapeutic drug monitoring and adherence to medicines studies, which would be helpful in decision making regarding treatment change in combination anti-retroviral therapies. (C) 2012 Elsevier B.V. All rights reserved.