Multiplexed therapeutic drug monitoring (TDM) of antiviral drugs by LC-MS/MS

被引：13
作者：
Conti, M. [1 ]
Cavedagna, T. Matulli [1 ]
Ramazzotti, E. [1 ]
Mancini, R. [1 ]
Calza, L. [2 ]
Rinaldi, M. [2 ,3 ]
Badia, L. [2 ,3 ]
Guardigni, V [2 ]
Viale, P. [2 ]
Verucchi, G. [2 ,3 ]
机构：
[1] Azienda USL Bologna, LUM Metropolitan Lab, Bologna, Italy
[2] Alma Mater Studiorum Univ Bologna, Dept Med & Surg Sci, Infect Dis Unit, Bologna, Italy
[3] Alma Mater Studiorum Univ Bologna, Res Ctr Study Hepatitis, Bologna, Italy
来源：
CLINICAL MASS SPECTROMETRY | 2018年 / 7卷
关键词：
Ribavirin; Directly acting antiviral drugs (DAAs); Hepatitis C virus (HCV); Hepatitis C; Therapeutic drug monitoring (TDM); Dried plasma spots (DPS); HEPATITIS-C; PROTEASE INHIBITOR; ACTING ANTIVIRALS; HUMAN PLASMA; UPLC-MS/MS; RIBAVIRIN; BOCEPREVIR; QUANTITATION; ASUNAPREVIR; VALIDATION;
D O I：
10.1016/j.clinms.2017.12.002
中图分类号：
R446 [实验室诊断]; R-33 [实验医学、医学实验];
学科分类号：
1001 ;
摘要：
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.
引用
收藏
页码：6 / 17
页数：12
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