人血浆中瑞格列奈HPLC法测定及其药代动力学研究

目的建立了人血浆中瑞格列奈浓度的HPLC测定方法，研究瑞格列奈在人体中药物动力学行为。方法血浆样品经酸化后，用醋酸乙酯提取，色谱柱为C18Shim-packCLC-ODS，流动相为0.10mol/L柠檬酸-醋酸钠缓冲液（pH4.0）-甲醇(27∶73)(v/v)。紫外检测波长243nm。测定了22名受试者单剂量口服瑞格列奈4mg后血药浓度-时间过程。结果最低检测浓度2.5ng/ml,回收率大于90%,日间和日内的变异系数小于15%,线性范围为2.5～100.0ng/ml，符合生物样品分析的要求。受试者口服瑞格列奈片4mg后,估算的末端相半衰期0.83±0.31h,峰时间0.75±0.41h,峰浓度53.32±24.94ng/ml,MRT1.58±0.41h,AUC4074.95±30.57ng

Determination ofRepaglinide in Plasma by HPLC and Its Pharmacokinetics in Men

AIM: To establish a reversed phase HPLC method for determinationof repaglinide and to study pharmacokentics of repaglinide in men. METHODS: After acidified, the drug was extracted from plasma with acetate ether. Shim-pack CLC-ODS C18 column was used. Mobile phase consisted of 27% 0.10 mol/L citrate acid-sodium acetate buffer(pH=4.0) and 73% methanol. The eluted peaks were detected by UV detector at 243 nm. RESULTS: The recoveries of repaglinide from plasma were larger than 90% and RSD% of intra-day and inter-day were smaller than 15%. Calibration curves were linear over 2.5～100.0 ng/ml(r=0.9992) and the minimum detection concentration was 2.5 ng/ml. The pharmcokinetics of repaglinide in 22 healthy subjects was studied. After oral administration of 4 mg repaglinide tablet, the pharmacokinetic parameters were estimated as follows: T1/2, 0.83±0.31 h, Tmax, 0.75±0.41h, Cmax, 53.32±24.94 ng/ml, MRT 1.58±0.41 h, and, 74.95±30.57 ng·h/ml. CONCLUSION: A reliable and rugged simultaneous HPLC assay for repaglinide was developed. The assay method was convenient for clinical laboratory.