An Accurate and Effective Method for Measuring Osimertinib by UPLC-TOF-MS and Its Pharmacokinetic Study in Rats

Molecules. 2018 Nov 6;23(11):2894. doi: 10.3390/molecules23112894.

Abstract

Osimertinib, a new-generation inhibitor of the epidermal growth factor, has been used for the clinical treatment of advanced T790M mutation-positive tumors. In this research, an original analysis method was established for the quantification of osimertinib by ultra-performance liquid chromatography with time of flight mass spectrometry (UPLC-TOF-MS) in rat plasma. After protein precipitation with acetonitrile and sorafinib (internal standard, IS), they were chromatographed through a Waters XTerra MS C18 column. The mobile phase was acetonitrile and water (including 0.1% ammonia). The relative standard deviation (RSD) of the intra- and inter-day results ranged from 5.38 to 9.76% and from 6.02 to 9.46%, respectively, and the extraction recovery and matrix effects were calculated to range from 84.31 to 96.14% and from 91.46 to 97.18%, respectively. The results illustrated that the analysis method had sufficient specificity, accuracy and precision. Meanwhile, the UPLC-TOF-MS method for osimertinib was successfully applied into the pharmacokinetics of SD rats.

Keywords: UPLC-TOF-MS; osimertinib; pharmacokinetics; rat.

MeSH terms

  • Acrylamides
  • Aniline Compounds
  • Animals
  • Chromatography, High Pressure Liquid / methods*
  • Male
  • Molecular Structure
  • Piperazines / blood*
  • Rats
  • Rats, Sprague-Dawley
  • Reproducibility of Results
  • Tandem Mass Spectrometry

Substances

  • Acrylamides
  • Aniline Compounds
  • Piperazines
  • osimertinib