Chromatographia

, Volume 66, Issue 1–2, pp 55–61 | Cite as

Determination of 5-n-Butyl-4-{4-[2-(1H-tetrazole-5-yl)-1H-pyrrol-1-yl]phenylmethyl}-2,4-dihydro-2-(2,6-dichloridephenyl)-3H-1,2,4-triazol-3-one, a New Angiotensin Type 1 Receptor Antagonist in Rat Plasma by LC-ESI-MS: Application to Pharmacokinetic Studies

  • Bei Yan
  • Guang-ji Wang
  • Jian-guo Sun
  • Fen-zhi Sun
  • Xiao-yu Li
  • Xiao-ming Wu
  • Jin-yi Xu
  • Yuan-ting Zheng
  • Hua Lv
Original

Abstract

A simple and sensitive reversed-phase LC-ESI-MS method to identify and quantitate 5-n-butyl-4-{4-[2-(1H-tetrazole-5-yl)-1H-pyrrol-1-yl]phenylmethyl}-2,4-dihydro-2-(2,6-dichloridephenyl)-3H-1,2,4-triazol-3-one (1b), a new Angiotensin II type 1 receptor antagonist in rat plasma has been developed and validated. Sample preparation used a simple liquid–liquid extraction with ethyl acetate. Separation was achieved by gradient elution on a C18 column. The mobile phase consisted of acetonitrile and water (0.05% triethylamine and 0.05% acetic acid) at a flow rate of 0.2 mL min−1. The detection utilized selected ion monitoring (SIM) in the negative mode at m/z 507.1 and m/z 407.2 for the deprotonated molecular ions of 1b and the internal standard irbesartan, respectively. The lower limit of quantification was reproducible at 5 ng mL−1 with 100 μL of plasma and the good linear was observed in the 5–500 ng mL−1 range. This concentration range corresponded well with the plasma concentrations of 1b in pharmacokinetic studies. Recoveries of 1b in rat plasma were 76.1, 74.6 and 79.0% at 5, 50 and 500 ng mL−1. The RSD of intra-assay and inter-assay variations were all less than 5%. This validated LC-ESI-MS assay is an economic, quick, precise and reliable method for the analysis of 1b in pharmacokinetic studies.

Keywords

Column liquid chromatography-mass spectrometry Pharmacokinetics Rat plasma Angiotensin II type 1 receptor antagonist 

Notes

Acknowledgments

The project was supported by the National Natural Science Foundation of People’s Republic of China (No. 30572228, 30630076) and Jiangsu Natural Science Foundation (BK2005098).

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Copyright information

© Friedr. Vieweg & Sohn Verlag/GWV Fachverlage GmbH 2007

Authors and Affiliations

  • Bei Yan
    • 1
  • Guang-ji Wang
    • 1
  • Jian-guo Sun
    • 1
  • Fen-zhi Sun
    • 1
  • Xiao-yu Li
    • 1
  • Xiao-ming Wu
    • 2
  • Jin-yi Xu
    • 2
  • Yuan-ting Zheng
    • 1
  • Hua Lv
    • 1
  1. 1.Key Laboratory of Drug Metabolism and PharmacokineticsChina Pharmaceutical UniversityNanjingChina
  2. 2.Department of Medicinal Chemistry, College of PharmacyChina Pharmaceutical UniversityNanjingChina

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