Aravagiri M, Marder S R, Wirshing D, Wirshing W C
Psychopharmacology Unit, University of California of Los Angeles, 90073, USA.
Pharmacopsychiatry. 1998 May;31(3):102-9. doi: 10.1055/s-2007-979308.
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.
本文描述了一种同时测定人血浆中利培酮（RSP）及其9-羟基代谢物（9-OH-RSP）的简单、灵敏且准确的方法。讨论了临床情况下RSP剂量与RSP及9-OH-RSP血浆浓度之间的关系。两种化合物通过用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来。在氰基柱上进行高效液相色谱分离，并用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，能够准确测定低至0.25 ng/ml浓度的RSP和9-OH-RSP。测定结果准确、精密且变异系数小于15%。常用的合并用药和其他抗精神病药物不干扰RSP或9-OH-RSP的分析。RSP和9-OH-RSP的个体间和个体内血浆浓度值存在很大差异。在接受RSP治疗的精神分裂症患者中，9-OH-RSP似乎是主要的循环活性部分，其血浆浓度平均比RSP高22倍。RSP/9-OH-RSP浓度比值表明，其中三名患者可能存在细胞色素P450酶CYP 2D6缺乏。RSP的血浆浓度与每日口服给药剂量之间呈弱相关（r = 0.4684，p = 0.01，n = 215）。然而，RSP的每日剂量与9-OH-RSP的血浆浓度（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）之间存在良好的相关性。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局之间的关系，而不仅仅是单独测量RSP。
