An HPLC-MS/MS method for quantitation of Gly-MCA in mouse plasma: Application to a pharmacokinetic study

J Pharm Biomed Anal. 2017 Nov 30:146:53-58. doi: 10.1016/j.jpba.2017.07.020. Epub 2017 Aug 12.

Abstract

A simple, sensitive and rapid method using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was developed and validated for quantification of glycine-β-muricholic acid (Gly-MCA) in mouse plasma for the first time. Plasma samples were pretreated with protein precipitation. The analyte and internal standard were separated on a Shimadzu Shim-pack XR-ODS column (4.6×50mm, 2.2μm) using 0.1% formic acid-water-methanol as mobile phase, with a runtime of 5min. Detection was performed using negative ion electrospray tandem mass spectrometry via multiple reaction monitoring (MRM) scan mode. The linear range was 5ng-2μg/ml (correlation coefficient >0.995) for Gly-MCA with a lower limit of quantitation of 5ng/ml. The intra-day and inter-day precision were less than 9.2% for the analyte and accuracy was from 0.4% to 7.0%. This analytical method was then successfully applied to a pharmacokinetic study of Gly-MCA following oral administration and intraperitoneal injection in mice.

Keywords: Gly-MCA; HPLC–MS/MS; Mice; Pharmacokinetics; Plasma.

MeSH terms

  • Animals
  • Cholic Acids / blood*
  • Cholic Acids / chemistry*
  • Chromatography, High Pressure Liquid / methods
  • Formates / chemistry
  • Glycine / blood*
  • Glycine / chemistry*
  • Male
  • Methanol / chemistry
  • Mice
  • Mice, Inbred C57BL
  • Plasma / chemistry*
  • Reproducibility of Results
  • Tandem Mass Spectrometry / methods
  • Water / chemistry

Substances

  • Cholic Acids
  • Formates
  • Water
  • formic acid
  • muricholic acid
  • Glycine
  • Methanol