Department of Pharmacy Practice, College of Pharmacy and Health Sciences, Texas Southern University, 3100 Cleburne Street, Houston, TX 77004, USA.
J Chromatogr B Analyt Technol Biomed Life Sci. 2010 Nov 15;878(30):3181-6. doi: 10.1016/j.jchromb.2010.09.016. Epub 2010 Sep 29.
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.
依曲韦林是一种非核苷类逆转录酶抑制剂（NNRTI），对 NNRTI 耐药的 HIV-1 具有活性。本研究建立并验证了一种用于大鼠血浆中依曲韦林分析的简单、灵敏、特异的 LC-MS/MS 方法，以伊曲康唑为内标。采用乙酸乙酯提取，在反相 XTerra MS C₁₈ 柱上进行色谱分离。以 2 mM 乙酸铵水溶液（含 0.1%甲酸，溶剂 A）和甲醇中 0.1%甲酸溶液（溶剂 B）为流动相，梯度洗脱，流速为 300 μL/min。采用正离子电喷雾电离进行串联质谱检测。阳性模式下，依曲韦林和内标的前体/产物离子（m/z）分别为 435.9→163.6 和 706.7→392.6。依曲韦林在大鼠血浆中的浓度范围为 1-100 ng/mL 时，校准曲线呈线性。日内和日间准确度和精密度均在±10%以内。该方法已成功用于大鼠动物模型中依曲韦林的药代动力学评价。
