反相高效液相色谱法测定环胞霉素全血浓度及药代动力学

环胞霉素(cyclosporine)是由11个氨基酸组成的一种环状多肽,具有选择性的免疫抑制作用,目前国内外已广泛用于各种器官移植及骨髓移植。环胞霉素口服吸收不完全,消除半衰期长,体内个体差异大,文献报道其相对生物利用度可从7.6～47.6%。环胞霉素血浓度过高将引起肝肾毒性及其他毒性反应,血浓度太低则影响疗效,病人将会出现排斥反

DETERMINATION OF CYCLOSPORINE IN WHOLE BLOOD BY REVERSED PHASE HIGH PERFORMANCE LIQUID CHROMATOGRAPHY

A specific method of analysis for cyclosporine in whole blood by HPLC was established by using a Micropak MCH-5 column (4×150 mm) and a mobile phase consisting of 86% CH₃OH (containing 2 mmol NaAc) and 14% H₂O. The temperature of the column was maintained at 60℃, and the UV detector was set at 210 nm. Quinine hydrochloride was used as internal standard. Whole blood sample was extracted with ether-hexane (85:15).The detection limit for cyclosporine was 20 ng/ml in whole blood. The standard curve was. linear (r=.9998) over 48.55～1456.50 ng/ml. The average recovery was 79.81±2.37%. The coefficient of variation was less than 3.24% for within day (n=4) and less than 5.90% for between days (n=6), respectively. The blood concentrations of rabbits (n=6) which took cyclosporine (30 mg/kg) orally was determined by this method. The results indicate that the data fitted a two-compartment open model, and the half-life (t 1/2β) was found to be 14.58±7.50 h.