@entity1215 (RIF) and @entity3109 (INH), first line drugs for the treatment of @entity378 , are known to cause hepatotoxicity as a serious adverse side effect. To further understand the pharmacokinetic parameters of these two drugs, we have developed and validated a rapid, sensitive and selective LC-MS/MS method for simultaneous quantification of RIF, INH and their metabolites @entity36957 (DRIF), acetylisoniazid (AcINH) and @entity68594 ( @entity20730 ). Analytes were extracted from 20 l of plasma using solid-phase extraction (SPE) followed by chromatographic separation on Zorbax SB-Aq column (50mm*4.6mm, particle size 5 m) using stepwise gradient elution of 5mM @entity6190 and 90% @entity1626 with 0.1% @entity5189 . Separation of all analytes was achieved in the total run time of 6min. The analytes were detected under positive ionization mode by multiple reaction monitoring (MRM) and quantification of analytes was performed by using @entity6189 -labelled internal standard. Excellent linearity (r(2)>= 0.995) was achieved for the analytes at different concentration ranges. The method was accurate (90-115%), precise (CV %<14) and specific. Matrix effect was in the range of 93-111% except for INA (40-42%) while recovery from SPE was reproducible (CV %<7.4) in the range of 60-86%. Post-preparative stability (48h, 6  C autosampler) and freeze-thaw stability (3 cycles) were assessed with mean recovered concentration of >85%. The method was successfully applied to a clinical study of 33 healthy subjects to evaluate the effect of concomitant of INH on the pharmacokinetic parameters of RIF as well as the segregation of the subjects into slow or fast acetylators of INH.

Development and validation of liquid chromatography tandem mass spectrometry method for simultaneous quantification of first line XXXX drugs and metabolites in human plasma and its application in clinical study.

@entity36957 :: ('MESH:C032393', 'Chemical') :: ['25-desacetylrifampicin'] @entity6190 :: ('MESH:C018824', 'Chemical') :: ['ammonium acetate'] @entity20730 :: ('CHEBI:73179', 'Chemical') :: ['INA'] @entity1626 :: ('MESH:C032159', 'Chemical') :: ['acetonitrile'] @entity3109 :: ('MESH:D007538', 'Chemical') :: ['isoniazid'] @entity68594 :: ('MESH:D007539', 'Chemical') :: ['isonicotinic acid'] @entity1215 :: ('MESH:D012293', 'Chemical') :: ['Rifampicin'] @entity6189 :: ('MESH:D003903', 'Chemical') :: ['deuterium'] @entity378 :: ('MESH:D014376', 'Disease') :: ['tuberculosis'] @entity5189 :: ('MESH:C030544', 'Chemical') :: ['formic acid']
@entity378 :: (MESH:D014376,Disease) :: ['tuberculosis']
