A sensitive and validated LC-MS/MS method for high-throughput determination of pomalidomide in human plasma and pharmacokinetic studies  

作　　者：Chang Shu Teng-Fei Li Duo Li Zhong-Qiu Li Xing-Hua Xia 

机构地区：[1]State Key Laboratory of Analytical Chemistry for Life Science,School of Chemistry and Chemical Engineering,Nanjing University,Nanjing 210023,China [2]Department of Pharmaceutical Analysis,School of Pharmacy,China Pharmaceutical University,Nanjing 210009,China [3]School of Pharmacy,Department of Clinical Pharmacology,Sir Run Hospital,Nanjing Medical University,Nanjing 211166,China

出　　处：《Chinese Chemical Letters》2022年第2期916-919,共4页中国化学快报（英文版）

基　　金：financial support from National Natural Science Foundation of China (No.81603072)。

摘　　要：Pomalidomide is an immunomodulatory agent (IMiD) that has been approved by the US Food and Drug Administration (FDA) for clinical treatment of patients with multiple myeloma.In this work,we developed a sensitive and validated LC-MS/MS method for high-throughput determination of pomalidomide over the range of 1.006-100.6 ng/mL(R^(2)=0.9991) in human plasma and pharmacokinetic studies.A liquid-liquid extraction method using ethyl acetate was applied to extract pomalidomide and afatinib (as an internal standard,IS) from human plasma.Chromatographic separation was performed on a Hedera ODS column (150 mm×2.1 mm,5μm) with security guard C18 column (4 mm×2.0 mm) at 40℃.Methanol and 10 mmol/L aqueous solution of ammonium acetate containing 0.1%formic acid were used as a gradient elution mobile phase,and the flow rate was 0.4 mL/min.A triple quadruple tandem mass spectrometer using multiplex reaction monitoring mode (MRM) with electrospray ionization (ESI) positive ionization was employed.The precursor to product ion transitions for the quantitative analysis of pomalidomide and the IS were m/z 274.2→163.1 and m/z 486.1→371.1,respectively.This established method has been validated according to regulatory guideline,and the results were all within the acceptance criteria.The validated LC-MS/MS method was successfully applied to analyze samples obtained from clinical pharmacokinetics study after oral administration of pomalidomide (4 mg) capsules in human.

关 键 词：POMALIDOMIDE Liquid-liquid extraction LC–MS/MS method PHARMACOKINETIC Human plasma 

分 类 号：R969.1[医药卫生—药理学] O657.63[医药卫生—药学]