Simple and accurate quantitative analysis of 20 anti-tuberculosis drugs in human plasma using liquid chromatography–electrospray ionization–tandem mass spectrometry

• Published in: Journal of pharmaceutical and biomedical analysis 2015-01, Vol.102, p.9-16
• Main Authors: Kim, Hyo-Ji, Seo, Kyung-Ah, Kim, Hyun-Mi, Jeong, Eun-Sook, Ghim, Jong Lyul, Lee, Seung Heon, Lee, Young Min, Kim, Dong Hyun, Shin, Jae-Gook
• Format: Article
• Language: English
• Subjects: Anti-tuberculosis drugs; Antitubercular Agents - blood; Chromatography, Liquid; Drug Monitoring - methods; Human plasma; Humans; Limit of Detection; Liquid chromatography (LC)–tandem mass spectrometry (MS/MS); Multi-drug resistant tuberculosis; Multiple reaction monitoring; Sensitivity and Specificity; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry; Tuberculosis, Multidrug-Resistant - blood
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2014.08.026

•Simultaneous analysis of 20 anti-tuberculosis drugs in human plasma.•Fast and simple sample treatments were applied.•LC–MS/MS analyses were performed in less than 13min.•Suitable for therapeutic drug monitoring for patients with tuberculosis. A simple and accurate liquid chromatography (LC)–tandem mass spectrometry (MS/MS) method for the quantitation of 20 anti-tuberculosis (anti-TB) drugs in human plasma, was developed as a tool for therapeutic drug monitoring. Two protein precipitation methods were adopted; one using methanol containing 0.13N HCl, for precipitation of amikacin, kanamycin, streptomycin and pyrazinamide, and the other using acetonitrile, for precipitation of preamoxicillin, ciprofloxacin, clarithromycin, clofazimine, cycloserine, ethambutol, ethionamide, isoniazid, levofloxacin, linezolid, moxifloxacin, p-aminosalicylic acid (PAS), prothionamide, rifabutin, rifampin and roxithromycin. Separation was performed either on an HILIC silica column or a reversed-phase dC18 column, with a gradient elution. Detection was carried out in multiple reaction-monitoring (MRM) mode. The calibration curves were linear over a 50-fold concentration range, with correlation coefficients (r) greater than 0.9969 for all anti-TB drugs. The intra- and inter-day precision was less than 14.3%, and the accuracy ranged between 84.8 and 113.0%. The developed method was successfully applied to the identification and quantitation of anti-TB drugs in patients with multi-drug resistant TB.