Journal
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
Volume 102, Issue -, Pages 9-16Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jpba.2014.08.026
Keywords
Anti-tuberculosis drugs; Liquid chromatography (LC)-tandem mass spectrometry (MS/MS); Human plasma; Multi-drug resistant tuberculosis; Multiple reaction monitoring
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Funding
- Korea Centers for Disease Control and Prevention [2013E3100300]
- National Research Foundation (NRF) grant - Korea government [R13-2007-023-00000-0]
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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 0.13 N 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. (C) 2014 Elsevier B.V. All rights reserved.
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