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

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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 0.1-100μg/ml with a correlation coefficient greater than 0.99. The lower limit of quantitation of TM-25659 in rat plasma was 0.1μg/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.

Original languageEnglish
Pages (from-to)47-52
Number of pages6
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume63
DOIs
StatePublished - 7 Apr 2012

Bibliographical note

Funding Information:
This research was supported by the Ministry of Knowledge Economy (Grant NO. 2011-10033279 ).

Keywords

  • LC-MS/MS
  • Method validation
  • Pharmacokinetics
  • Rat plasma
  • TM-25659

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