Foglia J P, Sorisio D, Kirshner M A, Mulsant B H, Perel J M
Clinical Pharmacology Program, University of Pittsburgh, Western Psychiatric Institute and Clinic, PA 15213, USA.
J Chromatogr B Biomed Appl. 1995 Jun 23;668(2):291-7. doi: 10.1016/0378-4347(95)00074-s.
An accurate, reliable method has been developed for the therapeutic monitoring of perphenazine (PPZ) and its major metabolites in human plasma samples. Steady-state plasma levels of PPZ and its metabolites were quantitated for 30 elderly patients (mean age: 75) undergoing concurrent treatment with nortriptyline (NT) and PPZ, doses ranging from 4 to 32 mg/day for PPZ. The assay was suitable with patients on concurrent medications, and smaller patient plasma volumes (1 ml) were used indicating sufficient sensitivity and specificity. After plasma extraction and separation on a Nucleosil 5-microns C18 column, the recoveries (mean +/- S.D.) of PPZ and its metabolites were determined; perphenazine 92 +/- 7.5%, deshydroxyethylperphenazine 81 +/- 7.2%, perphenazine sulfoxide 68 +/- 6.4%, and 7-hydroxyperphenazine 45 +/- 5.5%. The assay also had limits of quantitative detectability for PPZ and its metabolites as follows: perphenazine 0.5 ng/ml, deshydroxyethylperphenazine 1.0 ng/ml, perphenazine sulfoxide 0.5 ng/ml, and 7-hydroxyperphenazine 5 ng/ml. Inter-assay reproducibility (C.V.) for the quality controls and patient samples ranged from 18.8 to 2.4%. The sensitivity and reproducibility of this method should improve PPZ therapeutic drug monitoring and research on interactions in depressed geriatric patients.
已开发出一种准确、可靠的方法用于监测人血浆样本中奋乃静（PPZ）及其主要代谢产物。对30例同时接受去甲替林（NT）和PPZ治疗的老年患者（平均年龄：75岁）的PPZ及其代谢产物的稳态血浆水平进行了定量分析，PPZ的剂量范围为4至32毫克/天。该检测方法适用于同时服用多种药物的患者，并且使用较小体积的患者血浆（1毫升），表明具有足够的灵敏度和特异性。在血浆经提取并在Nucleosil 5微米C18柱上分离后，测定了PPZ及其代谢产物的回收率（平均值±标准差）；奋乃静为92±7.5%，去羟乙基奋乃静为81±7.2%，奋乃静亚砜为68±6.4%，7-羟基奋乃静为45±5.5%。该检测方法对PPZ及其代谢产物的定量检测限如下：奋乃静0.5纳克/毫升，去羟乙基奋乃静1.0纳克/毫升，奋乃静亚砜0.5纳克/毫升，7-羟基奋乃静5纳克/毫升。质量控制品和患者样本的批间重复性（变异系数）范围为18.8%至2.4%。该方法的灵敏度和重复性应能改善对老年抑郁症患者的PPZ治疗药物监测及相互作用研究。
