title: Absolute quantification of imipramine and its metabolites in vivo utilizing calibrators from radiolabeled in vitro incubations.
abstract: BACKGROUND
  We have demonstrated the use of a single-point calibration approach, derived from in vitro metabolite identification studies utilizing radiolabeled imipramine, that allows for the quantitation of metabolites from in vivo studies in the absence of metabolite synthetic standards.
  
  
  RESULTS
  From the in vivo study of imipramine in rats, the concentration of parent and metabolites were determined using the single-point calibration approach. Sixty seven percent of the dosed imipramine was recovered within 24 h, with 95 and 5% of drug-related material detected in feces and urine, respectively.
  
  
  CONCLUSIONS
  Using a novel single-point calibration approach from radiolabeled in vitro studies, we quantified metabolites in vivo and determined various disposition pathways.
authors: Pharmaceutical Candidate Optimization, Biocon Bristol Myers-Squibb R&D Center (BBRC), Syngene International Limited, Biocon Park, Plot 2 & 3, Bommasandra IV Phase, Bangalore - 560099, India.
authors: Priyadeep
authors: P
authors: Bhutani
authors: Pharmaceutical Candidate Optimization, Biocon Bristol Myers-Squibb R&D Center (BBRC), Syngene International Limited, Biocon Park, Plot 2 & 3, Bommasandra IV Phase, Bangalore - 560099, India.
authors: Devang
authors: D
authors: Shah
authors: Pharmaceutical Candidate Optimization, Biocon Bristol Myers-Squibb R&D Center (BBRC), Syngene International Limited, Biocon Park, Plot 2 & 3, Bommasandra IV Phase, Bangalore - 560099, India.|Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence, KS 66047, USA.
authors: Ninad
authors: N
authors: Varkhede
authors: Pharmaceutical Candidate Optimization, Biocon Bristol Myers-Squibb R&D Center (BBRC), Bristol-Myers Squibb India Ltd., Bangalore 560099, India.
authors: Sandhya
authors: S
authors: Mandlekar
authors: Pharmaceutical Candidate Optimization, Bristol-Myers Squibb, Pennington, NJ 08534, USA.
authors: Silvi
authors: S
authors: Chacko
authors: Pharmaceutical Candidate Optimization, Biocon Bristol Myers-Squibb R&D Center (BBRC), Syngene International Limited, Biocon Park, Plot 2 & 3, Bommasandra IV Phase, Bangalore - 560099, India.
authors: Murali
authors: M
authors: Subramanian
mesh_terms: D000818:Animals; D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods* / Q000592:standards; D007099:Imipramine / Q000378:metabolism*; D007553:Isotope Labeling; D008297:Male; D013058:Mass Spectrometry / Q000379:methods* / Q000592:standards; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012449:Safety
chemical_list: D007099:Imipramine
keywords: imipramine; mass balance; metabolite identification; metabolites in safety testing; radiolabeled studies; scaling factors; single-point calibrator