Quantitative determination of ICG-001 in rat plasma using HPLC-MS/MS: A pharmacokinetic study

J Pharm Biomed Anal. 2022 Sep 20:219:114949. doi: 10.1016/j.jpba.2022.114949. Epub 2022 Jul 16.

Abstract

Although ICG-001, chemically synthesised from a bicyclic β-turn peptidomimetic template, represents various pharmacological activities, no validated determination methods in biological samples have been reported. This study was designed to establish a quantitative determination method for ICG-001 in rat plasma using high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) to validate the analytical method, including stability, and to characterise its pharmacokinetic behaviour in rats. After simple protein precipitation with acetonitrile, ICG-001 was eluted on a reversed-phase column using a mobile phase of water and acetonitrile (3:7 v/v, including 0.1% formic acid). The protonated precursor ion [M+H]+ and the major fragment ion were confirmed at m/z 549.2 and 141.4, respectively, for ICG-001. ICG-001 was stable under bench and storage conditions. The analytical method met the criteria for Food and Drug Administration-validated bioanalytical methods, and was successfully applied to a pharmacokinetic study for the first time following subcutaneous and intravenous administration.

Keywords: HPLC-MS/MS; ICG-001; Pharmacokinetics; Rats.

MeSH terms

  • Acetonitriles
  • Animals
  • Bridged Bicyclo Compounds, Heterocyclic*
  • Chromatography, High Pressure Liquid / methods
  • Pharmaceutical Preparations
  • Pyrimidinones
  • Rats
  • Reproducibility of Results
  • Tandem Mass Spectrometry* / methods

Substances

  • Acetonitriles
  • Bridged Bicyclo Compounds, Heterocyclic
  • ICG 001
  • Pharmaceutical Preparations
  • Pyrimidinones