Open AccessDetermination of thalidomide concentration in human plasma by liquid chromatography-tandem mass spectrometry
Author(s) -
Nan Bai,
Xiaoling Cui,
Jin Wang,
ChunGuang Sun,
Hekun Mei,
Beibei Liang,
Yun Cai,
XiuJie Song,
Jingkai Gu,
Rui Wang
Publication year - 2012
Publication title -
experimental and therapeutic medicine
Language(s) - English
Resource type - Journals
eISSN - 1792-1015
pISSN - 1792-0981
DOI - 10.3892/etm.2012.847
Subject(s) - chromatography , chemistry , selected reaction monitoring , formic acid , analyte , mass spectrometry , electrospray ionization , liquid chromatography–mass spectrometry , triple quadrupole mass spectrometer , calibration curve , tandem mass spectrometry , detection limit , analytical chemistry (journal) , ammonium acetate , high performance liquid chromatography
A rapid, sensitive and specific analytical method based on high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed for the determination of thalidomide concentration in human plasma. The analyte and internal standard were extracted by liquid-liquid extraction with ether-dichloromethane (3:2, v/v) and separated on a TC-C(18) column using methanol-10 mM ammonium acetate-formic acid (60:40:0.04, v/v/v) as the mobile phase at a flow rate of 0.9 ml/min. The detection was performed using an API 4000 triple quadrupole mass spectrometer in the positive electrospray ionization (ESI) mode and completed within 3.0 min. The multiple reaction monitoring (MRM) transitions were m/z 259.1→84.0 for the analyte and m/z 195.9→138.9 for temozolomide. The calibration curve exhibited a linear dynamic range of 2-1500 ng/ml (r>0.9991). The intra-and inter-day precisions (as relative standard deviation; RSD) were 6.8-13.5% and 4.3-5.0% respectively and the accuracy (as relative error; RE) was 2.0-3.5%. The recoveries and matrix effects were satisfactory in all the biological matrices examined. This method was successfully used in a pharmacokinetic study of thalidomide in healthy male volunteers receiving an oral administration of a 200-mg dose.