大鼠血浆中环丙沙星的HPLC荧光分析检测法及其体内药物动力学研究

HPLC determination of ciprofloxacin with fluorescence detection in rat plasma and its pharmacokinetics study

建立测定大鼠血浆中环丙沙星的RP HPLC荧光检测法和研究其体内的药物动力学。以格帕沙星为内标 ,血浆样品经乙腈沉淀蛋白 ,取上清夜进行HPLC检测。流动相为 0 0 5mol/L磷酸盐缓冲液( pH3 0 )—乙腈—甲醇 ( 77∶13∶10 ,v/v/v) ,荧光检测 ,λEX=2 76nm ,λEM=448nm。血浆样品在 0 0 0 2 5～ 0 5μg/ml范围内线性关系良好 ,平均提取回收率为 97 1% ,日间和日内精密度RSD均小于 8 0 % ,最低检测限达到 1 0ng/ml。环丙沙星在大鼠体内的过程符合双隔室开放型一级吸收动力学模型、药动学参数分别为 :T1/2(ka) =0 44h ,T1/2 (α) =0 92h ,T1/2 ( β) =5 6 6h ,Tmax=1 0 4h ,Cmax=0 35 μg/ml,AUC =1 86h·μg/ml。

A sensitive and rapid RP-HPLC method with fluorescence detection was developed to determine ciprofloxacin in rat plasma and its pharmacokinetics was also investigated. Grepafloxacin was used as an internal standard, the deproteinization by acetonitrile was proposed to deal with plasma samples and supernatants were subject to HPLC. The mobile phase consisted of 0.05mol/L phosphate buffer (pH3.0), acetonitrile and methanol (77∶13∶10, v/v/v). The fluorescence detection λ EX 276 nm and λ EM 448 nm were used. The good linearity with the range from 0.0025 to 0.5μg/ml was achieved. The average extraction recovery rate was 97.1% and RSD of the same-day and between-days was<8.0%. The lowest detection limit was 1.0 ng/ml . The time course of mean plasma concentrations was simulated by 3p87 program and conformed to two compartments with first-rate absorption kinetics process. The estimated main pharmacokinetics parameters were as follows: T 1/2 (Ka)=0.44 h, T 1/2 (α)=0.92 h, T 1/2 (β)=5.66 h, T max =1.04 h, C max =0.35μg/ml, AUC=1.86 h·μg/ml.