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.
Abobo
Cyril V
CV
Department of Pharmacy Practice, College of Pharmacy and Health Sciences, Texas Southern University, 3100 Cleburne Street, Houston, TX 77004, USA.
Wu
Lei
L
John
Jyothy
J
Joseph
Mathew K
MK
Bates
Theodore R
TR
Liang
Dong
D
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