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

被引：4

作者：

Jiang, Fulin ^{[1
]}

Peng, Xiang ^{[2
]}

Cai, Dake ^{[3
]}

Wen, Dingsheng ^{[1
]}

Liu, Yao ^{[1
]}

Zhi, Min ^{[2
]}

Chen, Jiangying ^{[1
]}

Hu, Pinjin ^{[2
]}

Wang, Xueding ^{[1
]}

Gao, Yujie ^{[1
]}

Huang, Min ^{[1
]}

Gao, Xiang ^{[2
]}

Zhong, Guoping ^{[1
]}

机构：

[1] Sun Yat Sen Univ, Sch Pharmaceut Sci, Lab Drug Metab & Pharmacokinet, North Campus, Guangzhou, Guangdong, Peoples R China

[2] Sun Yat Sen Univ, Affiliated Hosp 6, Guangdong Gastrointestinal Hosp, Guangzhou, Guangdong, Peoples R China

[3] Guangdong Prov Engn Technol Res Inst Tradit Chine, Guangzhou, Guangdong, Peoples R China

来源：

BIOMEDICAL CHROMATOGRAPHY | 2018年 / 32卷 / 08期

基金：

中国国家自然科学基金;

关键词：

LC-MS; MS; metabolites; pharmacokinetics; thalidomide; TANDEM MASS-SPECTROMETRY; TERATOGENESIS; INHIBITOR; DISEASE;

D O I：

10.1002/bmc.4240

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页数：9

共 20 条

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