Bus-Kwasnik Katarzyna, Filist Monika, Rudzki Piotr J
Acta Pol Pharm. 2016 Nov;73(6):1487-1493.
Eplerenone (EPL), a selective aldosterone receptor antagonist, is indicated in the treatment of chronic heart failure and hypertension. It is hard to find a green assay among a few published methods for its determination in human plasma or serum. Following a liquid-liquid extraction with methyl t-butyl ether, eplerenone and isotope labelled eplerenone - used as an internal standard - were separated from the endogenous compounds on an Atlantis dCl8 column (150 x 3 mm, 3.0 [im). An isocratic elution with the mobile phase consisting of methanol and ammonium acetate (3 : 2, v/v) was used. A single quadrupole mass spectrometer was operated in positive electrospray ionization using the selected ion monitoring mode. The method is more environmentally-friendly than the previously reported assays. Acetonitrile in the mobile phase was replaced with methanol which is a removable solvent. Plasma sample volume was reduced to 250 pL which significantly decreased waste volume. Chlorinated solvents used previously for liquid-liquid extraction were eliminated and the safety of the laboratory staff was increased by eliminating diethyl ether. The method is characterized by a short analysis time, simple sample preparation and reduction of waste volume, which are important advantages when analyzing large numbers of samples. The method was validated according to international regulatory guidelines and may be applied to human pharmacokinetic studies following a single 25 or 50 mg oral dose.
依普利酮（EPL）是一种选择性醛固酮受体拮抗剂，用于治疗慢性心力衰竭和高血压。在已发表的几种人血浆或血清中依普利酮的测定方法中，很难找到一种绿色分析方法。用甲基叔丁基醚进行液液萃取后，依普利酮和用作内标的同位素标记依普利酮在Atlantis dCl8柱（150×3 mm，3.0μm）上与内源性化合物分离。使用由甲醇和醋酸铵（3:2，v/v）组成的流动相进行等度洗脱。单四极杆质谱仪在正电喷雾电离模式下运行，采用选择离子监测模式。该方法比先前报道的分析方法更环保。流动相中的乙腈被可去除的溶剂甲醇取代。血浆样品体积减少到250μL，这显著减少了废液体积。消除了先前用于液液萃取的氯化溶剂，通过消除乙醚提高了实验室工作人员的安全性。该方法的特点是分析时间短、样品制备简单且废液体积减少，这些在分析大量样品时是重要优势。该方法已按照国际监管指南进行验证，可应用于单次口服25或50 mg剂量后的人体药代动力学研究。
