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Determination of thalidomide by high performance liquid chromatography: plasma pharmacokinetic studies in the rat

Yang, Xiaoxia, Hu, Zeping, Chan, Sui Yung, Ho, Paul, Chan, Eli, Duan, Wei, Goh, Boon Cher and Zhou, Shufeng 2005, Determination of thalidomide by high performance liquid chromatography: plasma pharmacokinetic studies in the rat, Journal of pharmaceutical and biomedical analysis, vol. 39, no. 1, pp. 299-304.

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Title Determination of thalidomide by high performance liquid chromatography: plasma pharmacokinetic studies in the rat
Author(s) Yang, Xiaoxia
Hu, Zeping
Chan, Sui Yung
Ho, Paul
Chan, Eli
Duan, Wei
Goh, Boon Cher
Zhou, Shufeng
Journal name Journal of pharmaceutical and biomedical analysis
Volume number 39
Issue number 1
Start page 299
End page 304
Publisher Elsevier B.V.
Place of publication Amsterdam, The Netherlands
Publication date 2005-09-01
ISSN 0731-7085
Keyword(s) HPLC
thalidomide
pharmacokinetics
Summary A sensitive and simple high performance liquid chromatography (HPLC) method was developed and validated for the determination of thalidomide in rat plasma. Chromatography was accomplished with a reversed-phase Hypersil C18 column. Mobile phase consisted of acetonitrile-10 mM ammonium acetate buffer (pH 5.50) (28:72, v/v), at a flow rate of 0.8 ml/min. Thalidomide was monitored by ultraviolet detector at 220 nm and it gave a linear response as a function of concentration over 0.02–50 μM. The limit of quantitation in rat plasma was 0.50 ng (0.02 μM plasma concentration) with an aliquot of 20 μl. Results from a 3-day validation study indicated that this method allows for simple and rapid quantitation of thalidomide with excellent accuracy and reliability. Using this validated assay, the effect of coadministered irinotecan (CPT-11) on the plasma pharmacokinetics of thalidomide in rats was determined. Coadministration of CPT-11 (intravenously, 60 mg/kg) increased the maximum plasma concentration (Cmax) and area under the plasma concentration–time curve (AUC0–10 h) of thalidomide by 32.29 and 11.66%, respectively, as compared to the control, but none of the effect of CPT-11 was of statistical significance (P > 0.05). Concomitant CPT-11 also caused a 10.04% decrease in plasma clearance (CL) and 14.51% decrease in volume of distribution (Vd) (P > 0.05). These results suggest that coadministered CPT-11 did not significantly alter the plasma pharmacokinetics of thalidomide in rats. Further studies are warranted to explore the pharmacokinetic and pharmacodynamic interactions between CPT-11 and thalidomide.
Language eng
Field of Research 111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2005, Elsevier B.V.
Persistent URL http://hdl.handle.net/10536/DRO/DU:30009228

Document type: Journal Article
Collection: School of Medicine
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