Direct Analysis Of Abused Drugs In Hair Based On Thermal Desorption Ionization Mass Spectrometry

In recent years,the types and quantities of drug abuse have been continuously increasing,with traditional drug abuse still being relatively serious and new psychoactive substances constantly emerging and developing rapidly.The abuse of such drugs can cause schizophrenia,hallucinations,anesthesia,and other effects,easily leading to death.Moreover,the rapid mutation rate of new psychoactive substances presents characteristics such as networking,internationalization,and popularization,causing serious public health and social problems,and bringing great tests and challenges to drug control work in the new era.In toxicology or forensic investigations,compared to other biological samples,hair analysis has unique advantages such as non-invasive sample collection,stable presence of drug pathogens,information reflecting medication time and frequency,and ease of storage,making it a powerful tool for investigating drug abuse.Hair analysis usually uses traditional Gas Chromatography-Mass Spectrometry(GC-MS)or Liquid Chromatography-Mass Spectrometry(LC-MS/MS)techniques for detection.However,these traditional detection techniques require a large number of samples and complex sample pre-treatment,including derivatization,shearing,grinding,filtration,liquid-liquid extraction,and solid-phase extraction.The whole sample preparation analysis requires a long-time cycle.Faced with such a severe situation of drug abuse,relying on traditional detection methods can no longer meet the current detection requirements.This thesis proposes a simple and fast environmental ionization mass spectrometry technology,Thermal Desorption Ionization Mass Spectrometer(TDI-MS),based on environmental ionization mass spectrometry technology.It is applied to the direct analysis of abused drugs in hair,with fast analysis speed,low sample damage Advantages such as low impact from hair matrix and small sample size required.The main research contents include the following three aspects:1.Analysis of abused drugs such as methamphetamine in a single hair using TDI-MS techniqueThis thesis established a rapid and direct thermal desorption ionization mass spectrometry technique for analyzing poisons(drugs)in single hair.Fix a single hair on a heating plate,and under the action of high voltage and ionizing solvent,the drugs in the hair are rapidly thermally adsorbed and ionized,and then transferred to the mass spectrometry entrance for detection.Analysis of a hair sample can be completed in a few minutes.Firstly,we optimized the experimental parameters and established the optimal experimental conditions:heating plate temperature of about 110℃,ionization voltage of 3.5 kV,and ionization solvent of methanol:water(v/v,1:1).Then,under this condition,thermal desorption ionization mass spectrometry technology was applied to analyze and detect drugs such as methamphetamine,tramadol,and methadone in a single hair.At the same time,MALDI-MSI technology was used to analyze methamphetamine positive hair.The experimental results showed that TDI-MS technology did indeed achieve thermal desorption and ionization of drug molecules in hair,fully proving that this technology has certain application value and feasibility in directly analyzing drug abuse in single hair.This simple,fast,direct,and sample free TDI-MS technology provides a new research approach for forensic researchers to directly analyze drugs in hair.2.Characterization of the distribution of abused drugs such as methamphetamine and tramadol on hair by TDI-MS techniqueIn criminal cases,hair segmentation analysis has been proven to help understand the background of the case.Based on the principle of drugs entering the hair matrix through the blood and the hair growth rate(about 1 cm/month),hair segmentation can roughly estimate the time of drug intake by analyzing the distribution of drugs along the hair shaft,providing conclusive evidence of drug abuse and information on the frequency of drug abuse.Therefore,TDI-MS technology was used in the experiment to segment and analyze a single positive hair sample,characterizing the distribution of abused drugs such as methamphetamine and tramadol on the hair shaft.Firstly,TDI-MS technology was used to segment and analyze single hair samples of drug abuse,such as MAMP,ADB-BUTINACA,and tramadol,in units of 1 cm.Statistical analysis was conducted on the signal intensity of drug ions in each hair segment to infer the drug abuse situation of the subject for several consecutive months,and then to speculate on the time and mode of drug abuse,which is conducive to better characterizing the drug abuse situation in the hair.At the same time,the traditional LC-MS/MS method was used to validate each segment of hair that was positive for methamphetamine,and the signal intensity of each segment of hair was counted.The results showed that the drug signal intensity of the two methods showed a similar trend,further indicating that TDI-MS technology has the potential to trace the frequency of drug abuse in hair.3.Exploration and Study on Other Abuse Drugs in Hair using TDI-MS techniqueIn order to further explore the relationship between its number and signal strength,first,TDI-MS technology was used to carry out root analysis on the hair abused by tramadol,analyze and detect different amounts of hair,count the signal strength of tramadol and its metabolites in different amounts,further explore the relationship between the number of hair and signal strength,and determine that when the number of hair in the experiment is about 30～50,the signal ionic strength of the drug is the largest.At the same time,in order to further expand the analysis and research of other abused drugs in hair,TDI-MS technology was used to screen and analyze 200 positive hair samples for drug abuse.Due to the sensitivity of the analysis method and the influence of drug content in a single hair,TDI-MS technology was used in the experiment to analyze a bundle of hair(about 30～50 hairs)with different drug abusers.Wrap and fix a bundle of hair with aluminum foil,exposing it at a distance of 1 cm from the root of the hair for analysis and detection.The drugs and their metabolites in the hair rapidly undergo pyrolysis,desorption,ionization,and mass spectrometry under the action of high temperature,high pressure,and ionizing solvents.The experimental results showed that tetrahydrocannabinol,MDMB-4en-PINACA,ADB-BUTINACA and its metabolites N-dealkylation ADB-BUTINACA,tramadol and its metabolite O-demethyltramadol,ketamine and its metabolite norketamine,MDMA and its metabolite 4,5-methylenedioxy amphetamine,ephedrine and its metabolite dehydroxyephedrine,phentermine and its metabolite N-hydroxy phentermine Dimethyltryptamine(DMT)and its metabolites are hydroxylated with DMT and N-demethylated with DMT.In the detection of hair samples,the detection of drug metabolites is the key to confirming drug use.This technology can not only analyze and detect the pathogenic drugs in hair,but also detect the metabolites of their drugs in the organism,further improving the accuracy of the detection results and avoiding false positives in experimental results.However,this technology still has certain drawbacks,as it is limited by the sensitivity of relevant instruments,and cannot detect drug molecules with strong efficacy and low dosage,weak lipid solubility,low binding force with melanin,and low amount of drug deposited in hair.Therefore,in subsequent experiments,further optimization is needed to improve the sensitivity of the method,and the signal response of the target object can be improved by destroying the hair surface and spraying the derivative matrix.In summary,this thesis proposes a simple and fast TDI-MS technique,which has advantages such as fast analysis speed,low sample destruction,low impact on hair matrix,and low sample size required.Multiple drugs in a single hair can be analyzed and detected in a normal pressure environment,and the distribution of multiple drugs in a single hair can also be characterized on the hair shaft.And using this technology,multiple abused drugs and their metabolites in hair can be quickly and accurately analyzed.The required experimental cycle is short,the operation is simple,and it can be used for rapid screening of a large number of hair samples.It is also suitable for the analysis and detection of multiple drugs,providing a simple and rapid technical support for hair analysis and detection work.