title: Determination of a novel TAZ modulator, 2-butyl-5-methyl-6-(pyridine-3-yl)-3-[2'-(1H-tetrazole-5-yl)-biphenyl-4-ylmethyl]-3H imidazo[4,5-b]pyridine] (TM-25659) in rat plasma by liquid chromatography-tandem mass spectrometry.
abstract: TM-25659 compound, a novel TAZ modulator, is developed for the control of bone loss and obesity. TAZ is known to bind to a variety of transcription factors to control cell differentiation and organ development. A selective and sensitive method was developed for the determination of TM-25659 concentrations in rat plasma. The drug was measured by liquid chromatography-tandem mass spectrometry after liquid-liquid extraction with ethyl acetate. TM-25659 and the internal standard imipramine were separated on a Hypersil GOLD C18 column with a mixture of acetonitrile-ammonium formate (10 mM) (90:10, v/v) as the mobile phase. The ions m/z 501.2→207.2 for TM-25659 and m/z 281.0→86.0 for imipramine in multiple reaction monitoring mode were used for the quantitation. The calibration range was 0.1-100 μg/ml with a correlation coefficient greater than 0.99. The lower limit of quantitation of TM-25659 in rat plasma was 0.1 μg/ml. The percent recoveries of TM-25659 and imipramine were 98.6% and 95.7% from rat plasma, respectively. The intra- and inter-batch precisions were 3.17-15.95% and the relative error was 0.38-10.82%. The developed assay was successfully applied to a pharmacokinetic study of TM-25659 administered intravenously (10 mg/kg) to rats.
authors.affiliation: Drug Discovery Platform Technology Team, Medicinal Science Division, Korea Research Institute of Chemical Technology, Daejon 305-600, South Korea.
authors.forename: Sung Heum
authors.initials: SH
authors.lastname: Choi
authors.forename: Kyeong-Ryoon
authors.initials: KR
authors.lastname: Lee
authors.forename: Jae-Chun
authors.initials: JC
authors.lastname: Woo
authors.forename: Nak Jeong
authors.initials: NJ
authors.lastname: Kim
authors.forename: Dong Cheul
authors.initials: DC
authors.lastname: Moon
authors.forename: Eun Sook
authors.initials: ES
authors.lastname: Hwang
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Ahn
authors.forename: Myung Ae
authors.initials: MA
authors.lastname: Bae
authors.forename: Min-Sun
authors.initials: MS
authors.lastname: Kim
mesh_terms: D000085:Acetates / Q000737:chemistry; D000097:Acetonitriles / Q000737:chemistry; D000217:Acyltransferases; D000818:Animals; D019440:Anti-Obesity Agents / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D002138:Calibration; D002853:Chromatography, Liquid / Q000592:standards; D004355:Drug Stability; D005561:Formates / Q000737:chemistry; D007099:Imipramine / Q000737:chemistry; D007275:Injections, Intravenous; D057230:Limit of Detection; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D015203:Reproducibility of Results; D012997:Solvents / Q000737:chemistry; D053719:Tandem Mass Spectrometry / Q000592:standards; D013777:Tetrazoles / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: C572937:2-butyl-5-methyl-6-(pyridine-3-yl)-3-(2'-(1H-tetrazole-5-yl)-biphenyl-4-ylmethyl)-3H-imidazo(4,5-b)pyridine; D000085:Acetates; D000097:Acetonitriles; D019440:Anti-Obesity Agents; D050071:Bone Density Conservation Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D005561:Formates; D012997:Solvents; D013777:Tetrazoles; D014157:Transcription Factors; C030544:formic acid; C007650:ethyl acetate; D000217:Acyltransferases; C544439:Tafazzin protein, rat; D007099:Imipramine; C032159:acetonitrile