采用液相色谱-串联质谱法对抗病毒药物进行多重治疗药物监测（TDM）。
Multiplexed therapeutic drug monitoring (TDM) of antiviral drugs by LC-MS/MS.
作者信息
Conti M, Matulli Cavedagna T, Ramazzotti E, Mancini R, Calza L, Rinaldi M, Badia L, Guardigni V, Viale P, Verucchi G
机构信息
LUM Metropolitan Laboratory - Azienda USL Bologna, Bologna, Italy.
Infectious Diseases Unit, Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy.
出版信息
Clin Mass Spectrom. 2017 Dec 16;7:6-17. doi: 10.1016/j.clinms.2017.12.002. eCollection 2018 Jan.
BACKGROUND
Therapeutic drug monitoring (TDM) can be a useful tool in the clinical management of anti-hepatitis C virus (anti-HCV) drugs. Methods for the determination of various types of anti-HCV drugs in biological samples are, therefore, needed for clinical laboratories.
OBJECTIVE
In this work, employing the LC-MS/MS approach, we aimed to develop a multiplexed method for identification of the following anti-HCV drugs: Ribavirin (RBV), Boceprevir (BOC), Telaprevir (TVR), Simeprevir (SIM), Daclatasvir (DAC), Sofosbuvir (SOF) and its metabolite GS 331007 (SOFM) in liquid plasma and in dried plasma spots (DPSs).
METHOD
A single-step extractive-deproteinization was employed for both liquid plasma and DPSs. Reverse-phase liquid chromatography coupled with MRM detection was developed for multiplexed drug detection and quantification.
RESULTS
Sensitivities (expressed as LOQ) were 10 (±1.2), 10 (±4.9), 10 (±4.4), 10 (±4.4), 10 (±6.4), 10 (±3.4), 10 (±6.4) ng/ml for RBV, SOFM, SOF, DAC, BOC, TVR, and SIM, respectively; accuracy (expressed as BIAS%) was <10% for all drugs; reproducibility (intra- and inter-day CV%) was <10% for all drugs; dynamic range was 10-10,000 ng/ml for all drugs.
CONCLUSIONS
A novel, simple, rapid and robust LC-MS/MS multiplex assay for the TDM of various anti-HCV drugs that are currently in the clinic was successfully developed. Application to DPS samples enabled TDM to be used for outpatients as well.
背景
治疗药物监测（TDM）在抗丙型肝炎病毒（抗HCV）药物的临床管理中可能是一种有用的工具。因此，临床实验室需要用于测定生物样品中各种抗HCV药物的方法。
目的
在本研究中，我们采用液相色谱-串联质谱（LC-MS/MS）方法，旨在开发一种多重方法，用于鉴定以下抗HCV药物：利巴韦林（RBV）、波普瑞韦（BOC）、特拉匹韦（TVR）、simeprevir（SIM）、达卡他韦（DAC）、索磷布韦（SOF）及其代谢产物GS 331007（SOFM），用于液体血浆和干血浆斑（DPS）。
方法
对液体血浆和DPS均采用单步萃取-去蛋白法。开发了反相液相色谱结合多反应监测（MRM）检测用于多重药物检测和定量。
结果
灵敏度（以定量下限表示）分别为：RBV为10（±1.2）、SOFM为10（±4.9）、SOF为10（±4.4）、DAC为10（±6.4）、BOC为10（±4.4）、TVR为10（±3.4）、SIM为10（±6.4）ng/ml；所有药物的准确度（以偏差百分比表示）均<10%；所有药物的重现性（日内和日间变异系数）均<10%；所有药物的动态范围为10 - 10,000 ng/ml。
结论
成功开发了一种用于目前临床中各种抗HCV药物TDM的新型、简单、快速且稳健的LC-MS/MS多重检测方法。该方法应用于DPS样品使得TDM也可用于门诊患者。
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