Determination of thalidomide by high performance liquid chromatography: plasma pharmacokinetic studies in the rat.
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 microM. The limit of quantitation in rat plasma was 0.50 ng (0.02 microM plasma concentration) with an aliquot of 20 microl. 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 (C(max)) and area under the plasma concentration-time curve (AUC(0-10h)) 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 (V(d)) (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.
Yang
Xiaoxia
X
Department of Pharmacy, Faculty of Science, National University of Singapore.
Hu
Zeping
Z
Chan
Sui Yung
SY
Ho
Paul C
PC
Chan
Eli
E
Duan
Wei
W
Goh
Boon Cher
BC
Zhou
Shufeng
S
D000818:Animals; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013792:Thalidomide / Q000097:blood* / Q000493:pharmacokinetics
D013792:Thalidomide