Development of a supercritical fluid chromatography-tandem mass spectrometry method for the determination of lacidipine in beagle dog plasma and its application to a bioavailability study

J Chromatogr B Analyt Technol Biomed Life Sci. 2014 Jan 15:945-946:121-6. doi: 10.1016/j.jchromb.2013.11.029. Epub 2013 Nov 28.

Abstract

A simple, novel, rapid and sensitive supercritical fluid chromatography-tandem mass spectrometry (SFC-MS/MS) method was developed and validated for the determination of lacidipine in beagle dog plasma with nimodipine as internal standard. The method involved a simple liquid-liquid extraction method with tert-butyl methyl ether. The analytes were analyzed on an Acquity UPC(2) with a HSS C18 SB column (3mm×100mm, 1.8μm) set at 50°C. The mobile phase was carbon dioxide (≥99.99%) and methanol (92:8, v/v) at a flow rate of 2ml/min, the compensation solvent was methanol with 2% formic acid at a flow rate of 0.2ml/min and a total analysis time of 1.5min for each sample. The multiple reaction-monitoring mode was used for quantification of ion transitions at m/z 473.32→354.10 and 419.00→343.10 for lacidipine and internal standard, respectively. The linearity range of proposed method was 0.10-100ng/ml) (r(2)≥0.9990). The intra- and inter-day precision values were less than 15% and accuracy was from -0.83% to 3.27% at all quality control levels. The proposed method was successfully applied to a pharmacokinetic study of lacidipine in beagle dogs.

Keywords: Lacidipine; Pharmacokinetic; Plasma; SFC–MS/MS.

Publication types

  • Validation Study

MeSH terms

  • Animals
  • Antihypertensive Agents / blood*
  • Carbon Dioxide / chemistry
  • Chromatography, Supercritical Fluid / methods*
  • Dihydropyridines / blood*
  • Dogs
  • Limit of Detection
  • Liquid-Liquid Extraction
  • Tandem Mass Spectrometry / methods*

Substances

  • Antihypertensive Agents
  • Dihydropyridines
  • Carbon Dioxide
  • lacidipine