Identification Of Fentanyl New Psychoactive Substances And Its Application

In decade years,the abuse of fentanyl and its analogues has become a major issue worldwide.Fentanyl is a potent synthetic opioid and used as an analgesic and anesthetic.The structure of fentanyl is simple,which make it easy to derive new compounds.Furthermore,the fatalities have posed a public health threat because they are more potent,more dependent and with lower lethal dose.To establish an identical method for fentanyl analogues has become an urgent problem for forensic toxicology laboratories.However,there are few studies on comprehensive detection of fentanyl analogues in China.Therefore,the specific research contents of this paper are summarized as follows.1.Determination fentanyl new psychoactive substances and novel synthetic opioids in whole blood by LC-MS/MS and its application.The samples were extracted with ethyl acetate by LLE and separated by Waters ACQUITY UPLC HSS T₃ column?100 mm×2.1 mm,1.8?m?.The LODs ranged from 0.005 to 0.03 ng/mL,and LLOQs ranged from0.05 to 0.2 ng/mL.The method was shown to be liner over a concentration range of 0.2-40 ng/mL for fentanyl,norfentanyl and norcarfentanil and 0.05-40 ng/mL for all other target analytes.Moreover,the method was successfully applied to three cases.The sample volume was only 100?L and the run time was 8 min in this method.The present method is more simple,selective and sensitive than other methods and suitable for authentic cases.1.Determination fentanyl new psychoactive substances and novel synthetic opioids in hair by LC-MS/MS and its application.Hair samples?20 mg?were extracted by cryogenic grinding in an extraction medium consisting of methanol,acetonitrile,and 2 mmol/L ammonium formate?pH 5.3?.Following centrifugation of the samples,the analytes were separated using a Waters ACQUITY UPLC HSS T₃column.The LODs and LLOQs ranged from 0.5 to 2.5 pg/mg and from 2to 5 pg/mg,respectively.Furthermore,the method was applied to two cases.In a case with single dose,fentanyl was detected at the concentration of 8.02 pg/mg.In other case with multiple dose,hair sample was cut into 3 segments in which sufentanil was detected at the concentration ranged from 31.48 pg/mg to 183.9 pg/mg.This method contained 30 fentanyl analogues and 6 novel synthetic opioids,particularly 4 pairs of isomers.Compared with other reported papers,the number of compounds in the method was the most.In addition,the method also involved novel synthetic opioids in order to solve the analytical problem of fentanyl abuse with other drugs.In general,this method is selective,sensitive and has potential for use in the determination fentanyl and its analogues in forensic laboratories.3.The fragmentation pathways of fentanyl new psychoactive substances and novel synthetic opioids.Based on GC-HRMS and LC-HR-MS/MS,the fragmentation pathways of fentanyl new psychoactive substances and novel synthetic opioids were probed.In the ESI mode,fentanyl analogues mainly undergo piperidine ring degradation,phenethyl and piperidine ring dissociation,piperidine ring and amide moiety cleavage,while piperidine ring degradation and phenethyl-piperidine ring dissociation are the major pathways in the EI mode.The five novel synthetic opioids largely undergo amide group dissociation and N-cyclohexyl bond cleavage in the ESI mode.Compared with other papers,this study investigated characteristic fragment ions and pathways,which based on a large number of fentanyl analogues.Furthermore,the study also applied to an authentic case involving cyclopropylfentanyl.Thus,this work facilitates the detection and quantitation of fentanyl analogues and novel synthetic opioids or other substances with similar structures in forensic laboratories.In conclusion,this thesis developed some methods to identify fentanyl analogues and novel synthetic opioids.For known compounds,the efficient,rapid,selective and sensitive methods were developed and validated for simultaneous detection of fentanyl analogues and applied to authentic cases.For unknown compounds,based on the high resolution mass spectrometry and structures of known fentanyl analogues and novel synthetic opioids,the characteristic fragment ions and pathways were summarized and successfully applied to authentic cases.In summary,this study provided a support for the identification of fentanyl new psychoactive substances.