关键词: 氯法拉滨, HPLC, 大鼠, 药动学

Abstract: AIM: To establish an HPLC method for the determination of Clofarabine concentration in the plasma of rats and calculate the pharmacokinetic parameters.METHODS: All the samples were separated on a Agilent ODS Hypersil C18 analytical column(150 mm×4.6 mm,5 μm) by a mobile phase of acetonitrile-water(16∶84).The analytical column temperature was 30 ℃, the ultraviolet detection wavelength was at 263 nm, and the flow rate was 1.2 mL/min.The dosage of 30 mg/kg was used for the intravenous injection of Clofarabine before we took blood from each rat at 0.17, 0.33, 0.5, 0.75, 1.0, 1.5, 2.0, 4.0 and 8.0 h post administration. The plasma concentration of Clofarabine was measured by HPLC.RESULTS: The chromatographic peak of Clofarabine was separated completely with the impurities in rat plasma.Good linearity was found over the range of 0.05-20.0 μg/mL for Clofarabine determination (the linear equation was y=21.758x-0.9155, r=0.999910). The recovery of methodology was 95%~105%, the inter- and intra-day precisions were both less than 10%.The concentration time curve of Clofarabine in rat could be fitted to two compartment model, and the major pharmacokinetic parameters were as follows: A=14.20±2.45,B=1.81±0.51,CL =(2.91±0.47) L·h^-1·kg^-1,AUC_(0-t)=(10.22±1.88) mg·L^-1·h,t_1/2β=(2.03±0.16) h.CONCLUSION: This method is selective and sensitive for Clofarabine determination, and can also be used in pharmacokinetic research. The drug shows us a two-compartment model in rat plasma, and it's half-life in plasma of rats was 2 h.

Key words: Clofarabine, HPLC, Rat, Pharmacokinetics