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.

中文翻译：

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通过LC–MS / MS对抗病毒药物进行多重治疗药物监测（TDM）

背景

治疗药物监测（TDM）在抗丙型肝炎病毒（anti-HCV）药物的临床管理中可能是有用的工具。因此，临床实验室需要测定生物样品中各种类型的抗HCV药物的方法。

目的

在这项工作中，我们采用LC-MS / MS方法，旨在开发一种鉴定以下抗HCV药物的多重方法：利巴韦林（RBV），博西普韦（BOC），特拉普韦（TVR），西美普韦（SIM），达卡他韦（DAC），索非布韦（SOF）及其代谢产物GS 331007（SOFM）在血浆和干血浆斑点（DPS）中。

方法

血浆和DPS均采用一步萃取脱蛋白。开发了结合MRM检测的反相液相色谱用于多重药物检测和定量。

结果

灵敏度（以LOQ表示）为10（±1.2），10（±4.9），10（±4.4），10（±4.4），10（±6.4），10（±3.4），10（±6.4）ng / ml分别用于RBV，SOFM，SOF，DAC，BOC，TVR和SIM；所有药物的准确度（表示为BIAS％）均小于10％；所有药物的重现性（日内和日间CV％）均<10％；所有药物的动态范围为10–10,000 ng / ml。

结论

目前已成功开发出一种新颖，简单，快速且稳定的LC-MS / MS多重分析方法，用于多种抗HCV药物的TDM。将DDM应用于DPS样本后，TDM也可用于门诊病人。