Quantification of rilpivirine in human plasma, cervicovaginal fluid, rectal fluid and genital/rectal mucosal tissues using liquid chromatography-tandem mass spectrometry

Bioanalysis. 2014;6(14):1907-21. doi: 10.4155/bio.14.59.

Abstract

Background: A sensitive, specific and robust liquid chromatography-tandem mass spectrometry method has been developed and validated for the quantification of rilpivirine in human plasma, genital/rectal biofluids and mucosal tissues.

Methods: Plasma and tissue samples were extracted using protein precipitation (acetonitrile/water; 5:1 v/v), and genital/rectal biofluids absorbed onto ophthalmic swabs were extracted using liquid-liquid extraction (hexane/ethyl acetate; 80:20 v/v). A stable isotope-labeled internal standard ((13)C-d4-RPV) was used, and the assay was validated over a concentration range of 0.5-400 ng/ml.

Conclusion: Inter- and intra-assay precision and accuracy met the acceptance as per US FDA bioanalytical guidelines. The validated assay has been used for the determination of rilpivirine concentrations in these matrices as part of an exploratory pharmacokinetic study investigating the suitability of a long-acting formulation of rilpivirine for pre-exposure prophylaxis.

Publication types

  • Validation Study

MeSH terms

  • Anti-HIV Agents / analysis
  • Anti-HIV Agents / blood
  • Anti-HIV Agents / pharmacokinetics*
  • Body Fluids / metabolism
  • Chromatography, High Pressure Liquid / methods*
  • Female
  • Humans
  • Male
  • Mucous Membrane / metabolism
  • Nitriles / analysis
  • Nitriles / blood
  • Nitriles / pharmacokinetics*
  • Pyrimidines / analysis
  • Pyrimidines / blood
  • Pyrimidines / pharmacokinetics*
  • Reproducibility of Results
  • Rilpivirine
  • Tandem Mass Spectrometry / methods*

Substances

  • Anti-HIV Agents
  • Nitriles
  • Pyrimidines
  • Rilpivirine