The development and application of a novel LC-MS/MS method for the measurement of Dolutegravir, Elvitegravir and Cobicistat in human plasma

J Chromatogr B Analyt Technol Biomed Life Sci. 2016 Aug 1:1027:174-80. doi: 10.1016/j.jchromb.2016.05.040. Epub 2016 May 27.

Abstract

Dolutegravir and Elvitegravir belongs to a class of integrase inhibitors which has recently been approved by the FDA for the treatment of HIV-infection. Elvitegravir and its co-administered booster drug, Cobicistat, has shown the potential to be a candidate for a one pill once a day regimen and is currently a component of many clinical trials. A sensitive LC-MS/MS method has been developed and validated for the simultaneous determination of these three drugs in human plasma. A liquid- liquid extraction was used as a sample preparation technique using 100μL of plasma. The method was validated from 10 to 4000ng/mL for Dolutegravir, Elvitegravir and Cobicistat. Chromatography was performed on XBridge C18 2.1mm×50mm column, using an 80:20 methanol/water mobile phase containing 0.1% formic acid on a gradient program. This method was successfully applied for ongoing clinical trials.

Keywords: Cobicistat; Dolutegravir; Elvitegravir; LC–MS/MS; Method validation.

Publication types

  • Validation Study

MeSH terms

  • Anti-HIV Agents / blood*
  • Chromatography, High Pressure Liquid / methods*
  • Cobicistat / blood*
  • HIV Infections / drug therapy
  • HIV Integrase Inhibitors / blood
  • Heterocyclic Compounds, 3-Ring / blood*
  • Humans
  • Limit of Detection
  • Liquid-Liquid Extraction / methods
  • Oxazines
  • Piperazines
  • Pyridones
  • Quinolones / blood*
  • Tandem Mass Spectrometry / methods*

Substances

  • Anti-HIV Agents
  • HIV Integrase Inhibitors
  • Heterocyclic Compounds, 3-Ring
  • Oxazines
  • Piperazines
  • Pyridones
  • Quinolones
  • elvitegravir
  • dolutegravir
  • Cobicistat