Development and validation of an LCMS method to determine the pharmacokinetic profiles of caffeic acid phenethyl amide and caffeic acid phenethyl ester in male Sprague-Dawley rats

Biomed Chromatogr. 2014 Feb;28(2):241-6. doi: 10.1002/bmc.3011. Epub 2013 Aug 24.

Abstract

A validated LCMS method was developed for the quantitative determination of caffeic acid phenethyl amide (CAPA) and caffeic acid phenethyl ester (CAPE) from rat plasma. Separation was achieved using a reverse-phase C12 HPLC column (150 × 2.00 mm, 4 µm) with gradient elution running water (A) and acetonitrile (B). Mass spectrometry was performed with electrospray ionization in negative mode. This method was used to determine the pharmacokinetic profiles of CAPA and CAPE in male Sprague-Dawley rats following intravenous bolus administration of 5, 10 and 20 mg/kg of CAPA and 20 mg/kg of CAPE. The pharmacokinetic analysis suggests the lack of dose proportionality in the dose range of 5-20 mg/kg of CAPA. Total clearance values for CAPA ranged from 45 to 156 mL/min and decreased with increasing dose of CAPA. The volume of distribution for CAPA ranged from 17,750 to 52,420 mL, decreasing with increasing dose. The elimination half-life for CAPA ranged from 243.1 to 295.8 min and no statistically significant differences were observed between dose groups in the range of 5-20 mg/kg (p > 0.05). The elimination half-life for CAPE was found to be 92.26 min.

Keywords: LCMS; Sprague-Dawley rats; caffeic acid phenethyl amide; caffeic acid phenethyl ester; pharmacokinetics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caffeic Acids / blood*
  • Caffeic Acids / chemistry
  • Caffeic Acids / pharmacokinetics*
  • Chromatography, High Pressure Liquid / methods*
  • Chromatography, Reverse-Phase / methods
  • Limit of Detection
  • Linear Models
  • Male
  • Phenylethyl Alcohol / analogs & derivatives*
  • Phenylethyl Alcohol / blood
  • Phenylethyl Alcohol / chemistry
  • Phenylethyl Alcohol / pharmacokinetics
  • Rats
  • Rats, Sprague-Dawley
  • Reproducibility of Results
  • Spectrometry, Mass, Electrospray Ionization

Substances

  • Caffeic Acids
  • caffeic acid phenethyl amide
  • caffeic acid phenethyl ester
  • Phenylethyl Alcohol