奥氮平血药浓度的测定及其人体药代动力学

Determination of Olanzapine in Plasma by HPLC and Its Pharmacokinetics in Men

目的 建立测定人血浆中奥氮平浓度的HPLC-UV方法,研究健康受试者口服奥氮平片后的药代动力学。方法 以阿米替林为内标,血浆样品加维生素C抗氧化,经碱化后用乙醚-环已烷进行萃取。以0.01mol/L磷酸铵（pH4.0）-甲醇-乙腈（55:22.5:22.5）为流动相,采用Hypersil silica柱进行分离,紫外270nm处进行测定。结果 方法的专属性较好;低、中、高浓度（1.19,9.50,38.00ng/ml）的平均提取回收率分别为81.97,93.47和96.72。该法在1.19～38.00 ng/ml浓度范围内呈线性关系,最低检测浓度为1.19ng/ml,日内、日间RSD分别小于9％和12％。用此法测定了20名健康受试者单剂量po奥氮平片后的血药浓度经时变化过程。结论 该法灵敏度高,重现性好,操作简便,适用于临床药代动力学研究和血药浓度监测。

AIM To develop a sensitive HPLC-UV method for determination of olanzapine in human plasma and to study pharmacokinetics of olanzapine in men. METHODS After a single-step liquid-liquid extraction,the compound was separated on a normal-phase silica gel column using 0. 01 mol/L (NH4)3 PO4(pH 4. 0)-methanol-acetonitrile (55 = 22. 5:22. 5) mobile phase and measured by UV absorption at 270 nm. The addition of 0. 5% ascorbic acid to plasma protected olanzapine against oxidation during storage. The pharmacokinetics of olanzapine in 20 healthy subjects was studied after oral administration of lOmg. RESULTS The linear calibration curves were obtained in the concentration range of 1.19-38. 00 ng/ml and the minimum detection concentration was 1. 19 ng/ml. The average recoveries of olanzapine from plasma were larger than 90% and RSD% of intra-day and inter-day was smaller than 12%. After oral administration of 10 mg olanzapine tablet in 20 men, the main pharmacokinetic parameters were estimated as follows; T1/2K 31. 93±3. 25 h, Tmax4. 9±1. 7h, Cmax14. 49±2. 14 ng/ml. CONCLUSION The method is accurate, sensitive and suitable for clinical study of olanzapine.