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Concurrent determination of thalidomide in rat blood, brain and bile using multiple microdialysis coupled to liquid chromatography
Author(s) -
Huang YuJen,
Liao JyhFei,
Tsai TungHu
Publication year - 2005
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.466
Subject(s) - microdialysis , chemistry , thalidomide , chromatography , pharmacokinetics , high performance liquid chromatography , in vivo , jugular vein , pharmacology , medicine , biochemistry , extracellular , multiple myeloma , biology , microbiology and biotechnology
A rapid and sensitive system of liquid chromatography coupled with microdialysis was developed for the simultaneous determination of unbound thalidomide in rat blood, brain and bile for pharmacokinetic study. Microdialysis probes were concurrently inserted into the jugular vein toward the right atrium, the brain striatum and the bile duct of the anesthetized Sprague–Dawley rats for biological uid sampling after the administration of thalidomide (5 mg kg −1 ) through the femoral vein. Thalidomide and dialysates were separated using a Zorbax ODS C 18 column and a mobile phase comprising acetonitrile–methanol–0.1 m m 1‐octanesulufonic acid (32:3:65, v/v/v, pH 5.3) at ow rate of 1 mL min −1 . The UV wavelength was set at 220 nm. The concentration–response relationship was linear ( r 2 > 0.995) over a concentration range of 0.025–25 µg mL −1 . The intra‐assay and inter‐assay precision and accuracy of thalidomide fell within 7%. The average in vivo recoveries were 0.31 ± 0.02,0.046 ± 0.004 and 0.57 ± 0.02 ( n = 6), respective to the dialysates of blood, brain and bile, with thalidomide at concentrations 2, 5 and 10 µg mL −1 . The disposition of thalidomide in the blood, brain and bile uid suggests that there is a rapid thalidomide exchange and equilibration between the blood and brain systems. In addition, thalidomide undergoes hepatobiliary excretion. Copyright © 2005 John Wiley & Sons, Ltd.