A rapid and sensitive UHPLC-MS/MS assay for the determination of trelagliptin in rat plasma and its application to a pharmacokinetic study

J Chromatogr B Analyt Technol Biomed Life Sci. 2016 Oct 15:1033-1034:166-171. doi: 10.1016/j.jchromb.2016.08.024. Epub 2016 Aug 16.

Abstract

This study aims to develop and validate a simple, rapid and sensitive ultra-performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) method for exploring pharmacokinetic characteristics of trelagliptin. Protein precipitation by acetonitrile was used to prepare plasma sample. A RRHD Eclipse Plus C18 (2.1×50mm, 1.8μ) column with gradient mobile phase (containing acetonitrile and 0.1% formic acid) help to achieve the separation of trelagliptin and carbamazepine (IS) with high selectivity. Detection of target fragment ions m/z 358.2→133.9 for trelagliptin, and m/z 237.1→194.0 for IS was performed in positive-ion electrospray ionization mass spectrometry by multiple reaction monitoring. Linear calibration plots were achieved in the range of 5-4000ng/mL for trelagliptin (R(2)=0.999) in rat plasma. The recovery of trelagliptin ranged from 87.8% to 93.7%. The method was showed to be accurate, precise and stable. No obvious matrix effect was found. It has been fully validated and successfully applied to pharmacokinetic study of trelagliptin.

Keywords: Pharmacokinetics; Rat plasma; Trelagliptin; UHPLC–MS/MS.

MeSH terms

  • Animals
  • Chromatography, High Pressure Liquid / methods*
  • Drug Stability
  • Limit of Detection
  • Linear Models
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Reproducibility of Results
  • Tandem Mass Spectrometry / methods*
  • Uracil / analogs & derivatives*
  • Uracil / blood
  • Uracil / chemistry
  • Uracil / pharmacokinetics

Substances

  • Uracil
  • trelagliptin