A liquid chromatography-tandem mass spectrometry assay for quantification of rilpivirine and dolutegravir in human plasma

J Chromatogr B Analyt Technol Biomed Life Sci. 2014 Nov 15:971:1-9. doi: 10.1016/j.jchromb.2014.09.006. Epub 2014 Sep 16.

Abstract

A liquid chromatography-tandem mass spectrometry assay requiring a 100μL aliquot of human plasma for simultaneous determination of rilpivirine, a second generation non-nucleoside reverse transcriptase inhibitors of HIV and dolutegravir, a novel integrase stand transfer inhibitors of HIV concentrations has been developed. Sample pre-treatment is limited to protein precipitation with a mixture of methanol and zinc sulfate. After centrifugation the supernatant is injected in the chromatographic system, which consists of on-line solid phase extraction followed by separation on a phenyl-hexyl column. This 2.5min method, with its simple sample preparation provides sensitive (the limit of quantitation is 25ng/mL for each compound), accurate and precise (the intra-day and inter-day imprecision and inaccuracy are lower than 15%) quantification of the plasma concentration of these drugs and can be used for therapeutic drug monitoring in patients infected with HIV.

Keywords: Dolutegravir; Mass spectrometry; Rilpivirine.

MeSH terms

  • Anti-HIV Agents / blood*
  • Chemical Precipitation
  • Chromatography, High Pressure Liquid / methods
  • Chromatography, Liquid / instrumentation
  • Chromatography, Liquid / methods*
  • Drug Monitoring / methods
  • HIV Infections / blood
  • HIV Infections / drug therapy
  • HIV Integrase Inhibitors
  • Heterocyclic Compounds, 3-Ring / blood*
  • Humans
  • Nitriles / blood*
  • Oxazines
  • Piperazines
  • Pyridones
  • Pyrimidines / blood*
  • Reverse Transcriptase Inhibitors
  • Rilpivirine
  • Sensitivity and Specificity
  • Tandem Mass Spectrometry / instrumentation
  • Tandem Mass Spectrometry / methods*

Substances

  • Anti-HIV Agents
  • HIV Integrase Inhibitors
  • Heterocyclic Compounds, 3-Ring
  • Nitriles
  • Oxazines
  • Piperazines
  • Pyridones
  • Pyrimidines
  • Reverse Transcriptase Inhibitors
  • dolutegravir
  • Rilpivirine