Determination of Thalidomide by High Performance Liquid Chromatography: Plasma Pharmacokinetic Studies in the Rat
HPLC, thalidomide, pharmacokinetics
Digital Object Identifier (DOI)
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.
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Citation / Publisher Attribution
Journal of Pharmaceutical and Biomedical Analysis, v. 39, issues 1-2, p. 299-304
Scholar Commons Citation
Yang, Xiaoxia; Hu, Zeping; Chan, Sui Yung; Ho, Paul C.; Chan, Eli; Duan, Wei; Goh, Boon Cher; and Zhou, Shufeng, "Determination of Thalidomide by High Performance Liquid Chromatography: Plasma Pharmacokinetic Studies in the Rat" (2005). Pharmacy Faculty Publications. 16.