title: Concurrent determination of thalidomide in rat blood, brain and bile using multiple microdialysis coupled to liquid chromatography.
abstract: 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 fluid 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 mm 1-octanesulufonic acid (32:3:65, v/v/v, pH 5.3) at flow 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 microg 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 microg mL(-1). The disposition of thalidomide in the blood, brain and bile fluid suggests that there is a rapid thalidomide exchange and equilibration between the blood and brain systems. In addition, thalidomide undergoes hepatobiliary excretion.
authors.affiliation: Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Yu-Jen
authors.initials: YJ
authors.lastname: Huang
authors.forename: Jyh-Fei
authors.initials: JF
authors.lastname: Liao
authors.forename: Tung-Hu
authors.initials: TH
authors.lastname: Tsai
mesh_terms: D000818:Animals; D001646:Bile / Q000737:chemistry*; D001923:Brain Chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D008297:Male; D017551:Microdialysis / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013047:Specific Pathogen-Free Organisms; D013792:Thalidomide / Q000032:analysis* / Q000097:blood / Q000493:pharmacokinetics; D014466:Ultraviolet Rays
chemical_list: D013792:Thalidomide