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

Hyo Ji Kim, Kyung Ah Seo, Hyun Mi Kim, Eun Sook Jeong, Jong Lyul Ghim, Seung Heon Lee, Young Min Lee, Dong Hyun Kim, Jae Gook Shin

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)9-16
Number of pages8
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume102
DOIs
Publication statusPublished - 2015 Jan 5

Keywords

  • Anti-tuberculosis drugs
  • Human plasma
  • Liquid chromatography (LC)-tandem mass spectrometry (MS/MS)
  • Multi-drug resistant tuberculosis
  • Multiple reaction monitoring

ASJC Scopus subject areas

  • Analytical Chemistry
  • Pharmaceutical Science
  • Drug Discovery
  • Spectroscopy
  • Clinical Biochemistry

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