Plasma concentrations of risperidone and its 9-hydroxy metabolite and their relationship to dose in schizophrenic patients: Simultaneous determination by a high performance liquid chromatography with electrochemical detection
Plasma concentrations of risperidone and its 9-hydroxy metabolite and their relationship to dose in schizophrenic patients: Simultaneous determination by a high performance liquid chromatography with electrochemical detection
复制标题
DOI：
10.1055/s-2007-979308
复制
发表时间：
1998-05-01
影响因子：
4.3
通讯作者：
Wirshing, WC
中科院分区：
文献类型：
--
作者：
Aravagiri, M;Marder, SR;Wirshing, WC
描述了一种简单、灵敏且准确的同时测定人血浆中利培酮（RSP）及其9-羟基代谢物（9-OH-RSP）的方法。讨论了临床情况下RSP剂量与RSP和9-OH-RSP血浆浓度之间的关系。通过使用 15% 二氯甲烷的戊烷溶液进行简单的一步液-液萃取，从血浆中分离出这两种化合物。在氰基柱上进行高效液相色谱分离，并通过电化学检测器检测化合物。当使用 1 ml 血浆进行分析时，该方法具有足够的灵敏度，可以在浓度低至 0.25 ng/ml 时准确测定 RSP 和 9-OH-RSP。测定结果准确、精确且一致，变异系数小于 15%。常用的联合用药和其他抗精神病药物不会干扰 RSP 或 9-OH-RSP 的分析。RSP 和 9-OH-RSP 血浆浓度的个体间和个体内值存在很大差异。 9-OH-RSP 似乎是主要的循环活性部分，在接受 RSP 治疗的精神分裂症患者中，其血浆浓度平均比 RSP 高 22 倍。 RSP/9-OH-RSP 浓度比值表明，其中 3 名患者可能存在细胞色素 P450 酶 CYP 2D6 缺陷。 RSP 的血浆浓度与每日口服剂量的关系较弱（r = 0.4684，p = 0.01，n = 215）。然而，RSP 的日剂量与 9-OH-RSP 血浆浓度（r = 0.6654，p = 0.01，n = 280）或总活性部分、RSP 和 9-OH-RSP 浓度之和（r = 0.7041，p = 0.0005，n = 280）之间存在良好的关系。测量精神分裂症患者血浆中的总活性部分可能有助于评估剂量与血浆浓度之间的关系以及剂量与患者临床结果之间的关系，而不是单独测量RSP。
A simple, sensitive and accurate method for the simultaneous determination of risperidone (RSP) and its 9-hydroxy metabolite (9-OH-RSP) in human plasma is described. The relationship between dose of RSP and the plasma concentration of RSP and 9-OH-RSP in a clinical situation is discussed. Both compounds were isolated from plasma by a simple one-step liquid-liquid extraction with 15% methylene chloride in pentane. High-performance liquid chromatography separations were made on a cyano column and the compounds were detected by electrochemical detector. The method had sufficient sensitivity to determine RSP and 9-OH-RSP accurately at concentrations as low as 0.25 ng/ml when 1 ml of plasma is used for the analysis. The assay determinations were accurate, precise and consistent with a coefficient of variation less than 15%. Commonly co-administered drugs and other antipsychotics did not interfere with the analysis of either RSP or 9-OH-RSP There were large variations in inter- and intra-individual values of plasma concentrations of RSP and 9-OH-RSP. The 9-OH-RSP appears to be the major circulating active moiety and its plasma concentrations were, on the average 22 fold higher than that of RSP in schizophrenic patients treated with RSP. The ratio of RSP/9-OH-RSP concentrations suggested that three of the patients may have deficiency in cytochrome P450 enzyme CYP 2D6. The plasma concentrations of RSP showed a weak relationship with the administered daily oral dose (r = 0.4684, p = 0.01, n = 215). However, there was a good relationship between the daily dose of RSP and the plasma concentration of 9-OH-RSP (r = 0.6654, p = 0.01, n = 280) or the total active moiety, sum of RSP and 9-OH-RSP concentrations (r = 0.7041, p = 0.0005, n = 280). The measurement of the total active moiety in plasma of schizophrenic patients may be useful for assessing the relationship between dose and plasma concentration and dose and clinical outcome of patients rather than measuring RSP alone.