title: A novel LC-ESI-MS method for the simultaneous determination of etravirine, darunavir and ritonavir in human blood plasma.
abstract: 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.
authors.affiliation: Clinical Pharmacology/Analytical Chemistry Core, Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. naser2@unc.edu
authors.forename: Naser L
authors.initials: NL
authors.lastname: Rezk
authors.forename: Nicole R
authors.initials: NR
authors.lastname: White
authors.forename: Steven H
authors.initials: SH
authors.lastname: Jennings
authors.forename: Angela D M
authors.initials: AD
authors.lastname: Kashuba
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods; D000069454:Darunavir; D017320:HIV Protease Inhibitors / Q000097:blood*; D006801:Humans; D009570:Nitriles; D011724:Pyridazines / Q000097:blood; D011743:Pyrimidines; D019438:Ritonavir / Q000097:blood; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D013449:Sulfonamides / Q000097:blood; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D017320:HIV Protease Inhibitors; D009570:Nitriles; D011724:Pyridazines; D011743:Pyrimidines; D013449:Sulfonamides; C451734:etravirine; D019438:Ritonavir; D000069454:Darunavir