含阿片药物致民航安全敏感岗位人员毒品检测假阳性的快速识别研究

Drug of abuse has a profound influence on People's health and social security. Heroin is one of the most widespread abuse drugs in China. Its typical metabolites morphine and codeine can also be detected in many traditional Chinese medicine prescriptions. On the basis of the Chinese law, 156 thousand of civil aviation safety-sensitive employees must be accepted by the abuse drug testing. The established way of abuse drug testing is by utilizing the predominant metabolite, morphine, as the principal analytical target both in the screening and confirmation. Therefore, significant amount of "false positive" results were detected during abuse drug testing. These are caused by the used of traditional Chinese medicine prescriptions which contained opium alkaloids. By now, People who used the abuse drugs or taken the therapy opiates can't be rapidly and accurately distinguished using the existing technology. These seriously affected the employee's work and life, and influenced the productivity and efficiency of the airline. In this research, firstly comparative pharmacokinetics study between heroin and therapy opiates drugs in rats were established based on UPLC-MS/MS method for detecting the characteristic compounds (heroin, morphine, codeine, thebaine, narcotin, papaverine, cynaroside, glycyrrhizic acid and hyperine). Secondly, based on the above Pharmacokinetic parameters, we plan to establish the regression model between the opium alkaloids (morphine, codeine) and the traditional Chinese medicine prescriptions’ characteristic compounds (glycyrrhizic acid, hyperine). Thirdly, the fitting of regression model was calibrated with subjects’ samples (abuse drug users and traditional Chinese medicine prescriptions subjects). And the linked-pharmacokinetic model of the opiates-characteristic compounds was radiated. Finally, metabolites identification and pathway of heroin and therapy opiates drugs was studied by LC-QTOF-MS. In order to explore the marker metabolites, the difference of the metabolism fingerprint spectrum between heroin and therapy opiates drugs was also studied. Through the above studies, this project intends to provide the method and technology to easily distinguish heroin and therapy opiates drugs during the civil aviation drugs abatement work.

毒品危害人们身心健康和社会公共安全。根据我国法律，民航15.6万安全敏感岗位人员须定期接受毒品检测管理。海洛因是我国泛滥的毒品之一，其代谢产物吗啡、可待因在很多中药中含有。服用含阿片中药致毒品检测“假阳性”常有发生，现有的判别技术不能快速、准确区分，严重影响受检者工作生活，并干扰航空公司正常运行。本课题采用LC-MS/MS技术，研究大鼠使用海洛因、含阿片中药后，阿片类生物碱（吗啡、可待因、罂粟碱、蒂巴因、那可汀）、药物特征成分（木犀草苷、甘草酸、金丝桃苷等）的药动学特征，构建吗啡、可待因浓度-代谢时间-其他组分浓度回归模型；与志愿者使用中药、吸毒者生物样本中实测值进行比较校正，寻找灵敏稳定的联动标志物，建立多成分联动代谢方程；同时采用LC-QTOF-MS技术，研究使用中药、毒品后代谢指纹谱的差别，建立特征代谢标志物、多成分联动代谢合理浓度的毒品假阳性快速鉴别标准，研究结果主要用于民航。

毒品危害人们身心健康和社会公共安全。根据我国法律，民航等安全敏感岗位的从业人员须定期接受相关部门的毒品检测管理。目前，海洛因是我国最为泛滥的毒品，其代谢产物吗啡、可待因在中国的很多药品中含有，这给阿片类毒品检测工作带来了极大的干扰。本课题针对服用常规药物而造成毒品检测“假阳性”这一难题，建立快速判别和鉴别技术体系，主要研究内容如下：1）系统全面的研究含阿片复方中药制剂中主要化学成分的含量，从单品种复方甘草口服溶液中的7种化学成分的定量研究到16个品种、40批次复方中药制剂中18种化合物的定量分析，并对药物的含量差异进行统计分析和比较，为后期体内代谢研究提供基础。2）对复方甘草口服溶液和止咳宝片大鼠体内的代谢及药代动力学进行研究。模拟建立各组分PK 模型和药动学参数，比较单体同复方制剂中阿片类生物碱的药动学参数差异。3）采用UPLC-TOF-MS方法，结合数据挖掘技术、多变量统计分析，靶向验证研究建立海洛因滥用者的特征代谢产物。采用相关分析，对鉴定的代谢产物之间的关联性进行研究（p<0.001），最终筛选7个代谢产物入选靶向代谢产物组。同时收集16位海洛因滥用者和10名服用含阿片复方中药制剂人员的尿液进行验证，表面筛选代谢产物组可性，本方法可进行常规分析。.　　　本课题对含阿片的复方中药制剂的化学成分进行群表征，对服药和吸毒人员尿液中微量特征代谢产物进行有益探索，其研究结果目标代谢产物可以用于工作场所或强制性药物筛选中的辅助鉴定标准，也为“假阳性”鉴别体系的研究提供基础。