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

Sung Heum Choi; Kyeong-Ryoon Lee; Jae-Chun Woo; Nak Jeong Kim; Dong Cheul Moon; Eun Sook Hwang; Sung-Hoon Ahn; Myung Ae Bae; Min-Sun Kim

doi:10.1016/j.jpba.2012.01.036

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

J Pharm Biomed Anal. 2012 Apr 7:63:47-52. doi: 10.1016/j.jpba.2012.01.036. Epub 2012 Feb 7.

Authors

Sung Heum Choi¹, Kyeong-Ryoon Lee, Jae-Chun Woo, Nak Jeong Kim, Dong Cheul Moon, Eun Sook Hwang, Sung-Hoon Ahn, Myung Ae Bae, Min-Sun Kim

Affiliation

¹ Drug Discovery Platform Technology Team, Medicinal Science Division, Korea Research Institute of Chemical Technology, Daejon 305-600, South Korea.

PMID: 22357285
DOI: 10.1016/j.jpba.2012.01.036

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.

Publication types

Research Support, Non-U.S. Gov't
Validation Study

MeSH terms

Acetates / chemistry
Acetonitriles / chemistry
Acyltransferases
Animals
Anti-Obesity Agents / administration & dosage
Anti-Obesity Agents / blood*
Anti-Obesity Agents / pharmacokinetics*
Bone Density Conservation Agents / administration & dosage
Bone Density Conservation Agents / blood*
Bone Density Conservation Agents / pharmacokinetics*
Bridged Bicyclo Compounds, Heterocyclic / administration & dosage
Bridged Bicyclo Compounds, Heterocyclic / blood*
Bridged Bicyclo Compounds, Heterocyclic / pharmacokinetics*
Calibration
Chromatography, Liquid* / standards
Drug Stability
Formates / chemistry
Imipramine / chemistry
Injections, Intravenous
Limit of Detection
Male
Rats
Rats, Sprague-Dawley
Reference Standards
Reproducibility of Results
Solvents / chemistry
Tandem Mass Spectrometry* / standards
Tetrazoles / administration & dosage
Tetrazoles / blood*
Tetrazoles / pharmacokinetics*
Transcription Factors / metabolism*

Substances

2-butyl-5-methyl-6-(pyridine-3-yl)-3-(2'-(1H-tetrazole-5-yl)-biphenyl-4-ylmethyl)-3H-imidazo(4,5-b)pyridine
Acetates
Acetonitriles
Anti-Obesity Agents
Bone Density Conservation Agents
Bridged Bicyclo Compounds, Heterocyclic
Formates
Solvents
Tetrazoles
Transcription Factors
formic acid
ethyl acetate
Acyltransferases
Tafazzin protein, rat
Imipramine
acetonitrile