A validated LC-MS/MS method for the low-level determination of pemafibrate, a novel SPPARMα, in plasma

Bioanalysis. 2020 May;12(10):683-692. doi: 10.4155/bio-2020-0081. Epub 2020 Jun 3.

Abstract

Background: Pemafibrate, a novel selective peroxisome proliferator-activated receptor-α modulator, is prescribed for patients with dyslipidemia. To investigate other potential nonlipid-related effects of pemafibrate, the sensitive and rapid quantitation method for pemafibrate was required. Results: The developed LC-MS/MS assay method exhibited excellent accuracy, precision, sensitivity, stability, no matrix effect and high recovery. The LOQ (0.05 ng/ml) and run time (6.0 min) were superior to previous reports. The calibration curve showed good linearity over the wide concentration range (0.05-100.00 ng/ml). This validated method was successfully applied in a rat pharmacokinetic study using lower doses (0.02 or 0.10 mg/kg) than have been previously reported. Conclusion: This method can support gathering data for the evaluation of pemafibrate in future studies.

Keywords: SPPARMα; dyslipidemia; pemafibrate; selective PPARα modulator.

MeSH terms

  • Benzoxazoles / blood*
  • Benzoxazoles / pharmacology
  • Butyrates / blood*
  • Butyrates / pharmacology
  • Chromatography, Liquid
  • Humans
  • PPAR alpha / agonists
  • PPAR alpha / metabolism
  • Tandem Mass Spectrometry

Substances

  • (R)-2-(3-((benzoxazol-2-yl-d4 (3-(4-methoxyphenoxy-d7)propyl)amino)methyl)phenoxy) butanoic acid
  • Benzoxazoles
  • Butyrates
  • PPAR alpha
  • PPARA protein, human