Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH, United States.
J Pharm Biomed Anal. 2014 Jan;88:262-8. doi: 10.1016/j.jpba.2013.08.036. Epub 2013 Sep 2.
Pomalidomide was recently approved by the United States Food and Drug Administration for the treatment of patients with relapsed or refractory multiple myeloma who have received at least two prior therapies. As pomalidomide is increasingly evaluated in other diseases and animal disease models, this paper presents development and validation of a sensitive liquid chromatography tandem mass spectrometry assay for quantification of pomalidomide in mouse plasma and brain tissue to fill a gap in published preclinical pharmacokinetic and analytical data with this agent. After acetonitrile protein precipitation, pomalidomide and internal standard, hesperitin, were separated with reverse phase chromatography on a C-18 column with a gradient mobile phase of water and acetonitrile with 0.1% fomic acid. Positive atmospheric pressure chemical ionization mass spectrometry with selected reaction monitoring mode was applied to achieve 0.3-3000nM (0.082-819.73ng/mL) linear range in mouse plasma and 0.6-6000pmol/g in brain tissue. The within- and between-batch accuracy and precision were less than 15% for both plasma and brain tissue. The method was applied to measure pomalidomide concentrations in plasma and brain tissue in a pilot mouse pharmacokinetic study with an intravenous dose of 0.5mg/kg. This assay can be applied for thorough characterization of pomalidomide pharmacokinetics and tissue distribution in mice.
泊马度胺最近获得美国食品和药物管理局批准，用于治疗至少接受过两种先前治疗的复发或难治性多发性骨髓瘤患者。随着泊马度胺在其他疾病和动物疾病模型中的应用越来越广泛，本文提出了一种灵敏的液相色谱-串联质谱法，用于定量检测小鼠血浆和脑组织中的泊马度胺，以填补该药物在已发表的临床前药代动力学和分析数据中的空白。在乙腈蛋白沉淀后，泊马度胺和内标橙皮苷在 C18 柱上采用反相色谱分离，以水和含 0.1%甲酸的乙腈为梯度流动相。采用正大气压化学电离质谱，选择反应监测模式，实现了小鼠血浆中 0.3-3000nM（0.082-819.73ng/mL）和脑组织中 0.6-6000pmol/g 的线性范围。该方法在血浆和脑组织中的批内和批间准确度和精密度均小于 15%。该方法应用于静脉注射 0.5mg/kg 泊马度胺的小鼠药代动力学研究中，以测量血浆和脑组织中的泊马度胺浓度。该检测方法可用于全面研究泊马度胺在小鼠体内的药代动力学和组织分布。
