Riffel Kerry A, Groff Michelle A, Wenning Larissa, Song Hengchang, Lo Man-Wai
Department of Drug Metabolism, Merck Research Laboratories, West Point, PA 19486, USA.
J Chromatogr B Analyt Technol Biomed Life Sci. 2005 May 25;819(2):293-300. doi: 10.1016/j.jchromb.2005.02.013.
I, 2-{[5,7-dipropyl-3-(trifluoromethyl)-1,2-benzisoxazol-6-yl]oxy}-2-methyl propionic acid is an alpha peroxisome proliferator-activated receptor (PPAR) agonist with some gamma activity being investigated for potential use in the treatment of Type II diabetes mellitus and dyslipidemia. Two automated liquid-liquid extraction methods were developed and validated for the determination of I in human plasma. Concentrations of I were determined over a wide range of clinical doses. For Method A, plasma was acidified and extracted with ethyl acetate using a fully automated procedure. Analysis was performed by LC-MS/MS with a turbo ionspray source in negative ion mode. For Method B, a larger volume of plasma was extracted and a heated nebulizer source was used on the mass spectrometer. Method A was linear from 0.05 to 50 ng/mL and Method B from 0.2 to 1000 ng/mL. Validation procedures showed that both methods were robust, specific and reproducible.
我，2-{[5,7-二丙基-3-(三氟甲基)-1,2-苯并异恶唑-6-基]氧基}-2-甲基丙酸是一种α过氧化物酶体增殖物激活受体(PPAR)激动剂，具有一定的γ活性，目前正在研究其在治疗II型糖尿病和血脂异常方面的潜在用途。开发并验证了两种自动液-液萃取方法，用于测定人血浆中的我。在广泛的临床剂量范围内测定了我的浓度。对于方法A，血浆经酸化后，采用全自动程序用乙酸乙酯萃取。采用带涡轮离子喷雾源的LC-MS/MS在负离子模式下进行分析。对于方法B，萃取了更大体积的血浆，并在质谱仪上使用了加热雾化器源。方法A在0.05至50 ng/mL范围内呈线性，方法B在0.2至1000 ng/mL范围内呈线性。验证程序表明，这两种方法都具有稳健性、特异性和可重复性。
