1例不明原因多器官受损患者中毒原因多策略质谱技术确证  

Multi-strategic mass spectrometry technological confirmation of poisoning causes in a patient with unexplained multi-organ damage

作　　者：赵凌国 甄珍 杨莹[2] 雷蕾 涂云亮 马浩嘉 刘红河[3] 孙雯雯 ZHAO Lingguo;ZHEN Zhen;YANG Ying;LEI Lei;TU Yunliang;MA Haojia;LIU Honghe;SUN Wenwen(Baoan District Center for Disease Prevention and Control,Shenzhen,Guangdong 518101,China;Peking University Shenzhen Hospital,Shenzhen,Guangdong 518036,China;Shenzhen Center for Disease Prevention and Control,Shenzhen,Guangdong 518073,China;Shanghai AB Sciex Analytical Instrument Trading Company,Shanghai 200335,China)

机构地区：[1]深圳市宝安区疾病预防控中心,广东深圳518101 [2]北京大学深圳医院,广东深圳518036 [3]深圳市疾病预防控制中心,广东深圳518073 [4]上海爱博才思分析仪器贸易有限公司,上海200335

出　　处：《中国热带医学》2024年第5期612-617,共6页China Tropical Medicine

基　　金：广东省医学科学技术研究基金项目(No.A2021416);深圳市科技计划基础研究项目(No.JCYJ20220531093409021)。

摘　　要：目的调查1例不明原因导致多器官受损的中毒的原因,确证致病因子种类和暴露量,查明致病因子来源,为患者临床救治以及此类事件预防提供参考和依据。方法从患者长期服用的不明中药入手,首先用靶向策略进行筛查,考察是否为生物碱中毒,然后采用非靶向策略信息依赖采集模式(IDA)筛查患者血液、尿液和药物,结合可疑化合物的毒理作用和患者临床表现,确定致病因子。根据标准品建立定量方法,对全部样品中致病因子进行定量检测。流行病学调查获得患者服药史,结合药物规格及含量检测结果,确定各致病因子暴露量。最后采用数据非依赖序列窗口采集模式(SWATH)筛查全部样品,无偏采集化合物二级质谱信息,对已确证的致病因子进行验证和补充。结果靶向筛查排除常见生物碱中毒。患者血液、尿液均筛查出他达拉非,不明中成药检出他达拉非、西地那非、他达拉非甲基氯化物、扑热息痛和双氯芬酸,上述化合物副作用与患者临床表现相符。他达拉非、西地那非、他达拉非甲基氯化物、双氯芬酸和扑热息痛的长期日均暴露剂量最高分别为30.5、15.8、0.05、45.6和3.2 mg,严重过量。序列窗口采集模式同样筛查出上述5种药物,并检出盐酸巴马汀。结论本研究综合采用靶向筛查、非靶向筛查和靶向定量策略、数据依赖和数据非依赖采集模式,结合患者临床表现与流行病学资料,确定本例是由长期过量服用添加化学成分的中成药引起的药物中毒。本研究可为临床不明原因中毒患者诊断和调查提供思路,为相关中毒事件的应急检测和处置提供参考。Objective To investigate the cause of poisoning leading to multi-organ damage in a patient with an unexplained condition,to confirm the type and exposure amount of the pathogenic factor,to identify the sources of pathogenic factors,and to provide references and bases for the clinical treatment and the prevention of such events.Methods Starting with the unknown traditional Chinese medicine taken by patients for a long time,the targeted screening strategy was initially used to screen for alkaloid poisoning.Subsequently,a non-targeted screening strategy using Information-dependent Acquisition Mode(IDA)was used to screen the patient′s blood,urine,and drug samples.Combining the toxicological effects of suspected compounds with the patient′s clinical manifestations,the main pathogenic factors were determined.Quantitative methods were established according to standard substances to quantify the pathogenic factors in all the samples.An epidemiological investigation was conducted to obtain the patient′s medication history,and combined with the examination of the medication′s specifications and content,the exposure dose of each pathogenic factor was determined.Finally,a Data dataindependent acquisition(DIA)mode termed Sequential Window Acquisition of All Theoretical Fragment-Ion Spectra(SWATH)was used to screen all samples,unbiasedly collecting secondary mass spectrometry information of compounds,thereby verifying and supplementing the confirmed pathogenic factors.Results Targeted screening ruled out common alkaloid poisoning.Tadalafil was detected in the patient′s blood and urine.Tadalafil,sildenafil,chloropretadalafil,acetaminophen,and diclofenac were detected in unknown traditional Chinese medicine.The side effects of these compounds were consistent with the clinical manifestations of the patient.The highest daily average exposure doses of tadalafil,sildenafil,chloropretadalafil,acetaminophen,and diclofenac were 30.5 mg,15.8 mg,0.05 mg,45.6 mg,and 3.2 mg respectively,which were seriously excessive.The SWATH mo

关 键 词：中毒 非靶向筛查 靶向筛查 质谱 他达拉非 

分 类 号：R135.99[医药卫生—劳动卫生]