基于“咖啡环”效应的SERS技术用于氯氮平中毒的快速检测  

Antipsychoticdrug poisoning monitoring of clozapine in urine by using coffee ring effect based surface-enhanced Raman spectroscopy

作　　者：朱青霞 俞晓艳 吴泽兵 陆峰 原永芳[1] ZHU Qingxia;YU Xiaoyan;WU Zebing;LU Feng;YUAN Yongfang(Department of Pharmacy, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 201999, China;Department of Pharmaceutical Analysis, School of Pharmacy, Second Military Medical University, Shanghai, 200433, China)

机构地区：[1]上海交通大学医学院附属第九人民医院,上海市200199 [2]海军军医大学,上海市200433

出　　处：《光散射学报》2020年第2期108-120,共13页The Journal of Light Scattering

摘　　要：在药物中毒的病例中,抗精神病药物中毒占有较高的比例。临床医生在遇到这类中毒患者时,非常希望能对患者所服的药物进行快速定性、定量检测,指导对患者的救治。氯氮平是第一个非典型抗精神病药物,根据神经精神药理学与药物精神病学协会制定的精神科治疗药物监测(TDM)共识指南,有必要对服用氯氮平的患者进行TDM监测,从而及时调整剂量避免药物中毒现象的发生。本文旨在针对氯氮平中毒的尿液样品进行研究,并建立相应的检测方法。方法:利用表面增强拉曼光谱(SERS)技术对氯氮平中毒的大鼠尿样进行检测,采用薄层色谱法实现尿样中氯氮平及其代谢产物的分离纯化,借助“咖啡环”效应捕获更多的SERS热点,从而获得更稳定、灵敏的SERS检测方法。结果:本文建立了氯氮平的定量曲线y=0.0146x+0.3294,R2=0.9997,线性范围为0.5~50g/mL,该方法对氯氮平、去甲氯氮平、N-氧化氯氮平的最低检测浓度分别为1g/mL,0.04g/mL,5g/mL。利用该方法对大鼠尿液中的氯氮平进行定量检测,结果与LC-MS/MS方法基本一致。结论:该方法特异性强、灵敏度高、准确快速,可用于精神类药物中毒的快速筛查,将为TDM监测新技术研究提供一种新的思路。Antipsychotics are the drugs most often involved in drug poisoning cases,and therefore,therapeutic drug monitoring(TDM)for is necessary safe and effective medication administration of these drugs.In this study,a coffee ring effect-based surface-enhanced Raman spectroscopy(CRE-SERS)method was developed and successfully used to monitor antipsychotic poisoning by using urine samples for the first time.The established method exhibited excellent SERS performance since more hot spots were obtained in the“coffee ring”.Using the optimized CRE-SERS method,the sensitivity was improved one order more than that of the conventional method with reasonable reproducibility.The antipsychotic drug clozapine(CLO)spiked into urine samples at 0.5-50 g·mL^-1 was quantitatively detected,at concentrations above the thresholds for toxicity.The CRE-SERS method allowed CLO and its metabolites to be ultimately distinguished from real poisoning urine samples.The coffee-ring effect would provide more opportunities for practical applications of the SERS-based method.The frequent occurrence of drug poisoning may have created a new area for the application of the CRE-SERS method.It is anticipated that the developed method will also have great potential for other drug poisoning monitoring.

关 键 词：抗精神病药物中毒监测 氯氮平 表面增强拉曼光谱 “咖啡环”效应 尿液代谢物 

分 类 号：R74[医药卫生—神经病学与精神病学]