A novel LC-ESI-MS method for the simultaneous determination of etravirine, darunavir and ritonavir in human blood plasma

Talanta. 2009 Oct 15;79(5):1372-8. doi: 10.1016/j.talanta.2009.06.005. Epub 2009 Jun 9.


The new potent combination of antiretrovirals etravirine, darunavir, and ritonavir requires a new bioanalytical method for clinical pharmacology investigations and potential therapeutic drug monitoring. The development and validation of a novel LC-MS method for the simultaneous quantification of the most recently FDA-approved protease inhibitor and non-nucleoside reverse transcriptase inhibitor is described. This novel method was developed and validated using a sub-2 microm particle column, and provides excellent chromatographic separation and peak shape for all three analytes and internal standard. The method was validated over the range of 0.002-2.0 microg/mL. Intra- and inter-day accuracy of all analytes ranged from 88 to 106%, and intra- and inter-day precision was <7%. Dilution of samples 2-, 5-, and 10-fold maintained accuracy and precision, using a sample volume as low as 10 microL. Finally, the applicability of the method was investigated with clinical samples and external quality assurance proficiency testing samples.

Publication types

  • Research Support, N.I.H., Extramural
  • Validation Study

MeSH terms

  • Chromatography, High Pressure Liquid / methods
  • Darunavir
  • HIV Protease Inhibitors / blood*
  • Humans
  • Nitriles
  • Pyridazines / blood
  • Pyrimidines
  • Ritonavir / blood
  • Spectrometry, Mass, Electrospray Ionization / methods
  • Sulfonamides / blood
  • Tandem Mass Spectrometry / methods


  • HIV Protease Inhibitors
  • Nitriles
  • Pyridazines
  • Pyrimidines
  • Sulfonamides
  • etravirine
  • Ritonavir
  • Darunavir