title: Ex vivo conversion of prodrug prothionamide to its metabolite prothionamide sulfoxide with different extraction techniques and their estimation in human plasma by LC-MS/MS.
abstract: BACKGROUND
  The present work reports an ex vivo conversion study of prothionamide to its active metabolite prothionamide sulfoxide in human plasma during sample preparation by three conventional extraction techniques.
  
  
  RESULTS
  The chromatography was done on a Hypersil™ Gold C18 (50 × 2.1 mm, 3.0 µm) column using 0.1% acetic acid and acetonitrile (20:80, v/v) as the mobile phase. Quantitation of the analytes was done by MS/MS in the positive ionization mode. The method was validated over a wide concentration range of 30 to 6000 ng/ml for prothionamide and 50 to 10,000 ng/ml for prothionamide sulfoxide. The recovery for both the analytes was greater than 89%. Stability was extensively validated under different storage conditions.
  
  
  CONCLUSIONS
  The extraction protocol was optimized using acetonitrile as protein precipitant for their simultaneous determination in human plasma by LC-MS/MS. The method was applied to a bioequivalence study of 250 mg prothionamide tablet formulation in 14 healthy Indian subjects.
authors: Chemistry Department, Kadi Sarva Vishwavidyalaya, Sarva Vidyalaya Campus, Sector 15/23, Gandhinagar 382015, India.
authors: Vikas
authors: V
authors: Trivedi
authors: Vivek
authors: V
authors: Upadhyay
authors: Gaurang
authors: G
authors: Shah
authors: Manish
authors: M
authors: Yadav
authors: Pranav S
authors: PS
authors: Shrivastav
authors: Mallika
authors: M
authors: Sanyal
mesh_terms: D000995:Antitubercular Agents / Q000097:blood* / Q000737:chemistry* / Q000493:pharmacokinetics; D002853:Chromatography, Liquid / Q000379:methods; D015195:Drug Design; D006801:Humans; D009161:Mycobacterium / Q000378:metabolism; D011355:Prodrugs / Q000737:chemistry* / Q000493:pharmacokinetics; D011515:Prothionamide / Q000031:analogs & derivatives* / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D000995:Antitubercular Agents; D011355:Prodrugs; D011515:Prothionamide