LC-MS/MS determination of etravirine in rat plasma and its application in pharmacokinetic studies.
Etravirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that is active against NNRT-resistant HIV-1. A simple, sensitive, and specific LC-MS/MS method was developed and validated for the analysis of etravirine in rat plasma using itraconazole as the internal standard. The analytes were extracted with ethyl acetate and chromatographed on a reverse-phase XTerra MS C₁₈ column. Elution was achieved with a mobile phase gradient varying the proportion of a 2 mM ammonium acetate aqueous solution containing 0.1% formic acid (solvent A) and a 0.1% formic acid in methanol solution (solvent B) at a flow rate of 300 μL/min. The analytes were monitored by tandem-mass spectrometry with positive electrospray ionization. The precursor/product transitions (m/z) in the positive ion mode were 435.9→163.6 and 706.7→392.6 for etravirine and the internal standard, respectively. Calibration curves were linear over the etravirine rat plasma concentration range of 1-100 ng/mL. The inter- and intra-day accuracy and precision were within ±10%. The assay has been successfully used for pharmacokinetic evaluation of etravirine using the rat as an animal model.
Department of Pharmacy Practice, College of Pharmacy and Health Sciences, Texas Southern University, 3100 Cleburne Street, Houston, TX 77004, USA.
Cyril V
CV
Abobo
Lei
L
Wu
Jyothy
J
John
Mathew K
MK
Joseph
Theodore R
TR
Bates
Dong
D
Liang
D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D009570:Nitriles; D011724:Pyridazines / Q000097:blood* / Q000493:pharmacokinetics; D011743:Pyrimidines; D051381:Rats; D017207:Rats, Sprague-Dawley; D018894:Reverse Transcriptase Inhibitors / Q000097:blood / Q000493:pharmacokinetics; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods*
D009570:Nitriles; D011724:Pyridazines; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors; C451734:etravirine