高效液相色谱法测定小诺霉素的血药浓度及药动学研究

High performance liquid chromatographic assay of micronomicin in serum and its pharmacokinetics

本文报道了用高效液相色谱(HPLC)测定小诺霉素血药浓度的方法及小诺霉素在12例中国健康志愿者中的药代动力学研究,并分别研究了老年人和青年人以及男性和女性对小诺霉素在体内处置的差异,为进一步正确合理应用小诺霉素提供了重要的数据。本法使用紫外检测器,C_(18)柱,检测限0.2ng,最小检测血药浓度达0.1μg/ml,线性范围1～20μg/ml,小诺霉素和内标氯氮平的保留时间分别为6.8min和8.3min。本法准确、灵敏、快速,适用于小诺霉素药代动力学研究和血药浓度常规监测,12例志愿者单剂量肌注小诺霉素90mg后,药时曲线经计算机自动拟合,符合二室开放模型。主要药动学参数为:T1/2β老年人5.9±2.2h;青年人4.9±2.2h;男性4.2±1.7h;女性6.6±2.5h。CL(ml/min·kg)老年人0.79±0.11;青年人1.06±0.27;男性0.92±0.17;女性0.9±0.3。

Serum concentration of micronomicin was determined by high performance liquid chromatography(HPLC). The difference in vivo disposition of micronomicin between male and female aged and young werestudied. A UV-detector and C_(18) column were used in the HPLC。The detection limit of micronomicin was0.2ng, the minimum detectable concentration was 0.4μg/ml, Retention time of mmicronomiein and internalstandard clozepine were 6.8 min and 8.3 min respectively. The method could be used for pharmacokineticstudy and therapeutic concentration monitoring of micronomicin. The pharmacokinetics of micronomicin wasstudied in 12 chinese healthy volunteers after a single intramuscular injection of 90mg. The results showedthat the pharmacokineties of micronomicin fitred with the two compartment open model. ImportantparameterswereT_(1/2)β(aged)=5.89±2.18h, T_(1/2)β(young)=4.94±2.17h, T_(1/2)β(male)=4.21±1.67h. T_(1/2)β(female)=6.63±2.5h, CL (ml/min/kg) aged: 0.787±0.113, young: 1.059±0.274,male: 0.918±0.173, female: 0.928±0.32.