title: Simple and accurate quantitative analysis of 20 anti-tuberculosis drugs in human plasma using liquid chromatography-electrospray ionization-tandem mass spectrometry.
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 0.13N 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.
authors.affiliation: Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Busan, Republic of Korea.
authors.forename: Hyo-Ji
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Busan, Republic of Korea.
authors.forename: Kyung-Ah
authors.initials: KA
authors.lastname: Seo
authors.affiliation: Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Busan, Republic of Korea.
authors.forename: Hyun-Mi
authors.initials: HM
authors.lastname: Kim
authors.affiliation: Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Busan, Republic of Korea.
authors.forename: Eun-Sook
authors.initials: ES
authors.lastname: Jeong
authors.affiliation: Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Busan, Republic of Korea.
authors.forename: Jong Lyul
authors.initials: JL
authors.lastname: Ghim
authors.affiliation: Division of Pulmonary, Sleep, and Critical Care Medicine, Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Republic of Korea.
authors.forename: Seung Heon
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Inje University Busan Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea.
authors.forename: Young Min
authors.initials: YM
authors.lastname: Lee
authors.affiliation: Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Busan, Republic of Korea. Electronic address: dhkim@inje.ac.kr.
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Busan, Republic of Korea. Electronic address: phshinjg@inje.ac.kr.
authors.forename: Jae-Gook
authors.initials: JG
authors.lastname: Shin
mesh_terms: D000995:Antitubercular Agents / Q000097:blood*; D002853:Chromatography, Liquid; D016903:Drug Monitoring / Q000379:methods*; D006801:Humans; D057230:Limit of Detection; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry; D018088:Tuberculosis, Multidrug-Resistant / Q000097:blood*
chemical_list: D000995:Antitubercular Agents
keywords: Anti-tuberculosis drugs; Human plasma; Liquid chromatography (LC)–tandem mass spectrometry (MS/MS); Multi-drug resistant tuberculosis; Multiple reaction monitoring