HPLC法测定氯氮平及去甲氯氮平血药浓度及临床应用  

Determination of Clozapine and N-desmethyl Clozapine by HPLC and Clinical Application

作　　者：李琰 陈颖 瞿发林 金婷 谭兴起 LI Yan;CHEN Ying;QU Fa-lin;JIN Ting;TAN Xing-qi(Department of Clinical Pharmacology,the 102nd Hospital of PLA,Changzhou 213003,China)

机构地区：[1]解放军102医院临床药学科,江苏常州213003

出　　处：《解放军药学学报》2018年第4期296-300,共5页Pharmaceutical Journal of Chinese People's Liberation Army

基　　金：南京军区医学创新课题基金资助项目;No.14ZX04

摘　　要：目的建立HPLC法同时测定氯氮平及其代谢物去甲氯氮平血药浓度,对102例精神分裂症住院患者进行血药浓度监测,并对结果进行分析。方法采用Lichrospher C18(150mm×4.6mm,5μm)色谱柱;流动相:0.03mol·ml^(-1)醋酸铵(pH 5.0)-甲醇(45∶55);流速:1ml·min^(-1);检测波长:254nm;柱温:30℃;进样量:20μl。以乙醚为提取剂。统计学处理采用SPSS19.0软件。结果氯氮平及去甲氯氮平血药浓度在10.0~2000.0ng·ml^(-1)范围内峰面积与其浓度呈良好线性关系;日内、日间精密度均小于15%;在102例患者血药浓度监测结果中,相同剂量下个体间血药浓度存在显著差异;去甲氯氮平与氯氮平比值为0.23~0.88,氯氮平、去甲氯氮平比值与氯氮平浓度存在一定相关性;性别与氯氮平血药浓度密切相关,但与去甲氯氮平浓度无明显相关性。结论该方法简单、快速、准确,适用于氯氮平及其代谢物去甲氯氮平的血药浓度监测,为患者提供个体化用药指导。Objective To establish a high-performance liquid chromatography（HPLC）method for simultaneous determination of the concentrations of clozapine and N-desmethyl clozapine in serum and to analyze the serum drug concentrations of 102 inpatients.Methods The chromatographic column was Lichrospher C18（150 mm×4.6 mm,5μm）.The mobile phase consisted of 30 mmol·L-1 ammonioum（pH 5.0）-methanol（45∶55）.The flow rate was 1.0 ml·min-1,detection wavelength was at 254 nm,column temperature was 30 ℃,and the injection volume was 20μl.Ether was used as the extracting solvent.SPSS19.0 software was used for statistical analysis.Results The calibration curves were linear in the range of 10.0-2000.0 ng·ml-1 for clozapine and N-desmethyl clozapine.The intra-day and inter-day variation（RSD）was less than 15%.By analyzing the therapeutic drug monitoring（TDM）data of clozapine and N-desmethyl clozapine in 102 cases,it was found that blood drug concentrations were significantly different between individuals.The ratio of N-desmethyl clozapine to clozapine was 0.23-0.88,and this ratio was correlated with the concentration of clozapine.Gender was significantly correlated with the blood drug concentration of clozapine.,but not with N-desmethyl clozapine.Serum clozapine and N-desmethyl clozapine were significantly and positively correlated with the dosage.However,there was significant difference in the serum concentrations between individuals at the same dose.Conclusion This method is simple,quick and accurate,which can be used for TDM and pharmacokinetics studies of clozapine and N-desmethyl clozapine.

关 键 词：氯氮平 去甲氯氮平 治疗药物监测 个体化给药 

分 类 号：R917[医药卫生—药物分析学]