A validated LC-MS/MS method for the simultaneous determination of thalidomide and its two metabolites in human plasma: Application to a pharmacokinetic assay

作者：Jiang, Fulin; Peng, Xiang; Cai, Dake; Wen, Dingsheng; Liu, Yao; Zhi, Min; Chen, Jiangying; Hu, Pinjin; Wang, Xueding; Gao, Yujie; Huang, Min; Gao, Xiang^*; Zhong, Guoping^*

来源：Biomedical Chromatography, 2018, 32(8): e4240.

DOI：10.1002/bmc.4240

• LC-MS
• MS
• metabolites
• pharmacokinetics
• thalidomide

An accurate and sensitive LC-MS/MS method for determining thalidomide, 5-hydroxy thalidomide and 5-hydroxy thalidomide in human plasma was developed and validated using umbelliferone as an internal standard. The analytes were extracted from plasma (100L) by liquid-liquid extraction with ethyl acetate and then separated on a BETASIL C-18 column (4.6x150mm, 5m) with mobile phase composed of methanol-water containing 0.1% formic acid (70:30, v/v) in isocratic mode at a flow rate of 0.5mL/min. The detection was performed using an API triple quadrupole mass spectrometer in atmospheric pressure chemical ionization mode. The precursor-to-product ion transitions m/z 259.1186.1 for thalidomide, m/z 273.2161.3 for 5-hydroxy thalidomide, m/z 273.2146.1 for 5-hydroxy thalidomide and m/z 163.1107.1 for umbelliferone (internal standard, IS) were used for quantification. The calibration curves were obtained in the concentrations of 10.0-2000.0ng/mL for thalidomide, 0.2-50.0ng/mL for 5-hydroxy thalidomide and 1.0-200.0ng/mL for 5-hydroxy thalidomide. The method was validated with respect to linear, within- and between-batch precision and accuracy, extraction recovery, matrix effect and stability. Then it was successfully applied to estimate the concentration of thalidomide, 5-hydroxy thalidomide and 5-hydroxy thalidomide in plasma samples collected from Crohn's disease patients after a single oral administration of thalidomide 100mg.

• 出版日期2018-8
• 单位中山大学