An alternating polarity switching assay for quantification of oxycodone and topiramate: An application of LC-MS/MS method in support to PK/PD study in rodents

J Chromatogr B Analyt Technol Biomed Life Sci. 2019 Jun 15:1118-1119:93-100. doi: 10.1016/j.jchromb.2019.04.044. Epub 2019 Apr 22.

Abstract

In mass spectrometry, compounds that have different ionization properties experience challenges in simultaneous analysis. In the present paper, the authors proposed a polarity switching (+ve and -ve) LC-MS/MS method to analyze oxycodone and topiramate in a single run. The developed method was validated in the range of 5-1000 ng/mL for oxycodone and 20-5000 ng/mL for topiramate as per the US FDA guidelines. The mass spectrometer was operated in multiple reaction monitoring (MRM) mode to analyze oxycodone and topiramate simultaneously using oxycodone-d6 and topiramate-d12 as internal standards, respectively. Sample preparation was performed in 96-well protein precipitation plates using acetonitrile. Processed samples were analyzed using a C18 column with a gradient mobile phase composed of 10 mm ammonium formate with 0.1% formic acid and acetonitrile. The method was validated for selectivity, specificity, linearity, precision and accuracy, dilution integrity and stability. After validation, this method was successfully applied to quantify oxycodone and topiramate in plasma of concomitantly treated Sprague Dawley (SD) rats.

Keywords: 96-well plates; Drug-drug interaction study; LC–MS/MS analysis; Oxycodone; Topiramate.

MeSH terms

  • Animals
  • Chromatography, Liquid / methods*
  • Linear Models
  • Male
  • Oxycodone / administration & dosage
  • Oxycodone / blood*
  • Oxycodone / chemistry
  • Oxycodone / pharmacokinetics
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Tandem Mass Spectrometry / methods*
  • Topiramate / administration & dosage
  • Topiramate / blood*
  • Topiramate / chemistry
  • Topiramate / pharmacokinetics

Substances

  • Topiramate
  • Oxycodone