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Simultaneous determination of first-line anti-tuberculosis drugs and their major metabolic ratios by liquid chromatography/tandem mass spectrometry

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dc.contributor.authorSong, Sang Hoon-
dc.contributor.authorJun, Sun Hee-
dc.contributor.authorPark, Kyoung Un-
dc.contributor.authorYoon, Yeomin-
dc.contributor.authorLee, Jae Ho-
dc.contributor.authorKim, Jin Q-
dc.contributor.authorSong, Junghan-
dc.date.accessioned2009-11-11T03:27:33Z-
dc.date.available2009-11-11T03:27:33Z-
dc.date.issued2007-03-07-
dc.identifier.citationRapid Commun Mass Spectrom. 2007;21(7):1331-8.en
dc.identifier.issn0951-4198 (Print)-
dc.identifier.urihttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17340570-
dc.identifier.urihttps://hdl.handle.net/10371/11889-
dc.description.abstractMonitoring of anti-tuberculosis drug concentrations and dose adjustment can be helpful in cases that show poor response to treatment. Here, we describe a method that can rapidly and simultaneously measure the blood concentrations of four anti-tuberculosis drugs (isoniazid, rifampicin, pyrazinamide, and ethambutol) and two major metabolic ratios (acetylisoniazid/isoniazid and 25-desacetylrifampicin/rifampicin) using high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS). A C18 reversed-phase column and gradients of methanol in 0.3% formic acid and water were used for HPLC separation. The drug concentrations were determined by multiple reaction monitoring in positive ion mode and the assay performance was evaluated. We determined peak concentration ranges for each drug and acetylisoniazid/isoniazid and 25-desacetylrifampicin/rifampicin ratios by analyzing 2-h post-dose samples in patients treated with standard dosing as a first-line treatment. The preparation of 20 samples including two steps of deproteinization with 50% and 100% methanol was performed within 20 min and chromatographic separation was achieved within 4 min/sample. Interassay calibration variability data obtained over concentrations of 0-8 microg/mL for isoniazid and ethambutol and 0-80 microg/mL for rifampicin and pyrazinamide showed a linear and reproducible curve. Within-run and between-run imprecision (CVs) were 1.9-5.5% and 3.5-10.5% and the lower limits of detection and quantification were 0.01-0.5 microg/mL and 0.05-1.0 microg/mL, respectively. The isoniazid concentration was found to be inversely correlated to the acetylisoniazid/isoniazid ratio (R=-0.739, P<0.001). The devised method allows for the simple, rapid, sensitive and reproducible quantification of isoniazid, rifampicin, pyrazinamide, ethambutol and their two metabolic ratios and should be helpful for therapeutic drug monitoring in tuberculosis patients.en
dc.language.isoenen
dc.publisherJohn Wiley & Sonsen
dc.subjectAntitubercular Agents/*blood/*pharmacokineticsen
dc.subjectBlood Chemical Analysis/*methodsen
dc.subjectChromatography, High Pressure Liquid/*methodsen
dc.subjectComplex Mixtures/blooden
dc.subjectHumansen
dc.subjectIsoniazid/*analogs & derivatives/blooden
dc.subjectRifampin/*analogs & derivatives/blooden
dc.subjectSpectrometry, Mass, Electrospray Ionization/*methodsen
dc.titleSimultaneous determination of first-line anti-tuberculosis drugs and their major metabolic ratios by liquid chromatography/tandem mass spectrometryen
dc.typeArticleen
dc.contributor.AlternativeAuthor송상훈-
dc.contributor.AlternativeAuthor전선희-
dc.contributor.AlternativeAuthor박경운-
dc.contributor.AlternativeAuthor윤여민-
dc.contributor.AlternativeAuthor이재호-
dc.contributor.AlternativeAuthor김진규-
dc.contributor.AlternativeAuthor송정한-
dc.identifier.doi10.1002/rcm.2961-
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