An UPLC-MS/MS method for the quantitation of vortioxetine in rat plasma: Application to a pharmacokinetic study

J Chromatogr B Analyt Technol Biomed Life Sci. 2015 Aug 1:997:70-4. doi: 10.1016/j.jchromb.2015.05.010. Epub 2015 Jun 5.

Abstract

In this work, a simple, sensitive and fast ultra performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the quantitative determination of vortioxetine in rat plasma. Plasma samples were processed with a protein precipitation. The separation was achieved by an Acquity UPLC BEH C18 column (2.1mm×50mm, 1.7μm) column with a gradient mobile phase consisting of 0.1% formic acid in water and acetonitrile. Detection was carried out using positive-ion electrospray tandem mass spectrometry via multiple reaction monitoring (MRM). The validated method had an excellent linearity in the range of 0.05-20ng/mL (R(2)>0.997) with a lower limit of quantification (0.05ng/mL). The extraction recovery was in the range of 78.3-88.4% for vortioxetine and 80.3% for carbamazepine (internal standard, IS). The intra- and inter-day precision was below 8.5% and accuracy was from -11.2% to 9.5%. No notable matrix effect and astaticism was observed for vortioxetine. The method has been successfully applied to a pharmacokinetic study of vortioxetine in rats for the first time, which provides the basis for the further development and application of vortioxetine.

Keywords: Pharmacokinetics; Plasma; Rat; UPLC–MS/MS; Vortioxetine.

MeSH terms

  • Animals
  • Chromatography, High Pressure Liquid / methods*
  • Linear Models
  • Male
  • Piperazines / blood*
  • Piperazines / chemistry
  • Piperazines / pharmacokinetics*
  • Rats
  • Rats, Sprague-Dawley
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Sulfides / blood*
  • Sulfides / chemistry
  • Sulfides / pharmacokinetics*
  • Tandem Mass Spectrometry / methods*
  • Vortioxetine

Substances

  • Piperazines
  • Sulfides
  • Vortioxetine