基于全自动二维液相色谱的精神疾病靶症状的氯氮平有效血药浓度实验研究  

Study of clozapine plasma concentration for mental disease target symptoms

作　　者：曲衎衎 张晨宁 王姝姗 杜志强 张忠东 QU Kankan;ZHANG Chenning;WANG Shushan;DU Zhiqiang;ZHANG Zhongdong(The Affiliated Wuxi Mental Health Center With Nanjing Medical University,Wuxi Tongren Rehabilitation Hospitall,Nanjing Medical University,Jiangsu Wuxi 214151,China;School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 102488,China)

机构地区：[1]南京医科大学附属无锡精神卫生中心,无锡市同仁康复医院,江苏无锡214151 [2]北京中医药大学中药学院,北京102488

出　　处：《沈阳药科大学学报》2019年第10期926-933,共8页Journal of Shenyang Pharmaceutical University

基　　金：无锡市卫生计生委科研面上资助项目(MS201805);2018年无锡市科技发展医疗卫生指导性资助项目.

摘　　要：目的建立全自动二维液相色谱法(2D-LC-UV)测定血清中氯氮平浓度,探讨氯氮平有效血药浓度与不同精神疾病靶症状(精神分裂症阳性、阴性、混合型,双相障碍躁狂相及躁狂症)的关系。方法200μL进样,在一维柱Aston SX1色谱柱(25 mm×4.6 mm,5μm)上初步分离,通过中间柱Aston SCB(10 mm×4.6 mm,5μm)截取保留,并在二维柱Aston SCB(100 mm×4.6 mm,5μm)上进一步分离,直至最终测定。监测2015年7月—2017年6月我院的100例精神分裂症、双相障碍及躁狂症患者的血清中氯氮平的血药浓度,结合临床用药情况及疗效,分析不同靶症状的氯氮平有效血药浓度范围。结果本色谱条件下,氯氮平在64.47~1031.52μg·L^-1内线性关系良好。治疗精神分裂症阳性症状时氯氮平有效血药浓度范围为200~500μg·L^-1,精分症阴性症状有效血药浓度范围为50~200μg·L^-1;精分症混合型有效血药浓度范围为100~450μg·L^-1,双相障碍躁狂相及躁狂症有效血药浓度范围为150~450μg·L^-1。结论所建立的2D-LC-UV方法快速、准确,可用于氯氮平血清药物浓度研究。根据氯氮平有效血药浓度治疗不同的精神疾病靶症状,对临床个体化合理用药具有指导意义。Objective To establish a 2 D-LC-UV method to determine Clozapine,in order to study the relationship between Clozapine serum concentration and target symptoms of mental disease(positive,negative,mixed type of schizophrenia,manic phase of bipolar disorder as well as mania).Methods The 200μL sample was directly injected and primarily separated on the 1 st Aston SX1 column(4.6 mm×25 mm,5μm),then trapped on Aston SCB column(4.6 mm×10 mm,5μm)and separated by Aston SCB(4.6 mm×100 mm,5μm).The serum concentration of Clozapine in 100 mental disease patients,which was collected from 2015.07 to 2017.06 was determined.Combined with clinical medication and effects,the serum concentration of Clozapine in different target symptoms was analyzed.Results Clozapine was separated completely in the system with linear calibration curve over the concentration range of 64.47-1031.52 ng·mL^-1.The effective serum concentration of Clozapine in positive symptom of schizophrenia was 200-500 ng·mL^-1,while in negative symptom was 50-200 ng·mL^-1.The effective serum concentration of Clozapine in mixed type of schizophrenia was 100-450 ng·mL^-1,while in manic phase of bipolar disorder or mania was 150-450 ng·mL^-1.Conclusion The 2 D-LC-UV method is fast,accurate and can be used for the serum concentration determination of Clozapine.Monitoring of Clozapine serum concentration,which was relative to different target symptoms of mental disease,was beneficial to individualized treatment of schizophrenia patients.

关 键 词：氯氮平 全自动二维液相色谱法 血药浓度 靶症状 

分 类 号：R969[医药卫生—药理学]