TY - JOUR
T1 - Determination of thalidomide by high performance liquid chromatography
T2 - Plasma pharmacokinetic studies in the rat
AU - Yang, Xiaoxia
AU - Hu, Zeping
AU - Sui, Yung Chan
AU - Ho, Paul C.
AU - Chan, Eli
AU - Duan, Wei
AU - Boon, Cher Goh
AU - Zhou, Shufeng
PY - 2005/9/1
Y1 - 2005/9/1
N2 - 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 (AUC 0-10 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 (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.
AB - 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 (AUC 0-10 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 (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.
KW - HPLC
KW - Pharmacokinetics
KW - Thalidomide
UR - http://www.scopus.com/inward/record.url?scp=23444456503&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=23444456503&partnerID=8YFLogxK
U2 - 10.1016/j.jpba.2005.02.041
DO - 10.1016/j.jpba.2005.02.041
M3 - Article
C2 - 16085147
AN - SCOPUS:23444456503
VL - 39
SP - 299
EP - 304
JO - Journal of Pharmaceutical and Biomedical Analysis
JF - Journal of Pharmaceutical and Biomedical Analysis
SN - 0731-7085
IS - 1-2
ER -