反相高效液相色谱法测定人血中利培酮及9-羟利培酮及其临床应用

Simultaneous Determination of Risperidone and 9-hydroxyrisperidone in Human Serum Using RP-HPLC and Its Clinical Application

目的：测定人血中利培酮及其活性代谢物９－羟利培酮浓度，探讨其临床意义。方法：采用 Ｈｙｐｅｒｓｉｌ ＯＤＳ－Ｃ１８色谱柱（２５０ ｍｍ × ４．６ ｍｍ ＩＤ，粒度 ５μｍ），以甲醇：水：三乙胺（７３：２６．５：０．５ ｖ／ｖ，冰醋酸调ｐＨ＝８）为流动相，流速 １ｍｌ·ｍｉｎ－１，在ＵＶ２８０ｎｍ处测定了１６例口服利培酮精神病患者血中利培酮及其活性代谢物９－羟利培酮浓度。结果：利培酮及 ９－羟利培酮在 １０－１００ μｇ·Ｌ－１范围内有良好线性关系（ｒ＝０．９９５０及ｒ＝０．９９３５）。方法回收率为９８．３％～１０２．１％，日内及日间变异系数小于 ６．７１％。在每日 ２－６ｍｇ剂量范围内， １６例患者利培酮及 ９－羟利培酮血液浓度分别为 １０．９～３８．８ μｇ·Ｌ－１及 １１．５９－４９．７ μｇ·Ｌ－１。结论：测定方法简便、准确、专一性强，可用于临床治疗药物监测及人体内药代动力学研究。在每日２～５ｍｇ剂量范围内，利培酮及９－羟利培酮血浓度随服药剂量的增加而升高。

OBJECTIV: To simultaneously determine the concentrations of risperidone and its main active metabolite 9-hydroxyrisperidone in serum of 16 psychotic patients. METHODS:Hypersil ODS-C 18 colunm was used as the stationary phase and a solution composed of methanol-water-triethylamine (73:36.5 :0.5,v/v, was adjusted to pH 8 with glacial acetic acid ) as the mobile phase with a flow rate of 1 .0 ml·min-1. The detection was performed at UV 280mm. RESULTS: The standard curve was linear within the concentration range of 10-100μg.L-1 of risperidone and 9-hydroxyrisperidone in serum (r=0.9950 and 0.9935). The recoveries of risperidone and 9-hydroxyrisperidone was between 98.3% to 102. 1%.The relative standard deviations for the within-day and the between-days variation were < 6.71 %. The risperidone and 9-hydroxyrisperidone serum concentrations of 16 psychotic patients were in the range of 10.9-38.8μg.L-1 and 11 .5-49.7 μg.L-1 respectively within the dose of 2-5mg a day. CONCLUSION: The assay method is simple, precise and usable for therapeutic risperidone monitoring and its pharmacokinetic studies. The concentration risperidon and its active metabolite 9-hydroxyrisperidon were proportionally increased within the dose of 2-5mg risperidone.