Development and validation of LC-MS/MS method for quantification of pseudolaric acid B from the root bark of Pseudolarix kaempferi in rat plasma: application to a pharmacokinetic study

J Pharm Biomed Anal. 2015 Apr 10:108:56-60. doi: 10.1016/j.jpba.2015.01.050. Epub 2015 Feb 7.

Abstract

Pseudolaric acid B (PAB), which is the main biologically active diterpene acid of Pseudolarix kaempferi, has presented anti-fungal, anti-tumor, anti-fertility, and anti-tubulin activities. In this study, a sensitive and selective liquid chromatography tandem mass spectrometry (LC-MS/MS) method with multiple-reaction monitoring mode was employed for quantification of PAB in rat plasma. The calibration curve was linear over the range of 0.86-288 ng/mL with correlation coefficient (r) greater than 0.995 for PAB, and the lower limit of quantification was 0.86 ng/mL in rat plasma. The accuracy of PAB was between -9.1% and 7.0% relative error, and precision ranged from 1.2 to 10.6% relative standard deviation. This method was successfully applied to the pharmacokinetic studies of PAB in Sprague-Dawley rats. After single intravenous administration of 2.0, 4.0, and 8.0mg/kg PAB to rats, the t1/2 were (16.1 ± 5.6), (30.0 ± 13.7), and (27.4 ± 5.3)min, respectively. The pharmacokinetics (C(2min), AUC) of PAB within the used dosage range were in accordance with linear pharmacokinetic characteristics.

Keywords: Liquid chromatography–tandem mass spectrometry; Pharmacokinetic study; Pseudolaric acid B; Pseudolarix kaempferi; Rat plasma.

Publication types

  • Validation Study

MeSH terms

  • Administration, Intravenous
  • Animals
  • Area Under Curve
  • Calibration
  • Chromatography, Liquid / methods*
  • Diterpenes / administration & dosage
  • Diterpenes / isolation & purification
  • Diterpenes / pharmacokinetics*
  • Dose-Response Relationship, Drug
  • Half-Life
  • Limit of Detection
  • Male
  • Pinaceae / chemistry*
  • Plant Bark
  • Plant Roots
  • Rats
  • Rats, Sprague-Dawley
  • Tandem Mass Spectrometry / methods*

Substances

  • Diterpenes
  • pseudolaric acid B