Full Characterisation of Heroin Samples Using Infrared Spectroscopy and Multivariate Calibration.

The analysis of heroin samples, before use in the protected environment of user centra, could be a supplementary service in the context of harm reduction. Infrared spectroscopy hyphenated with multivariate calibration could be a valuable asset in this context, and therefore 125 heroin samples were collected directly from users and analysed with classical chromatographic techniques. Further, Mid-Infrared spectra were collected for all samples, to be used in Partial Least Squares (PLS) modelling, in order to obtain qualitative and quantitative models based on real live samples. The approach showed that it was possible to identify and quantify heroin in the samples based on the collected spectral data and PLS modelling. These models were able to identify heroin correctly for 96% of the samples of the external test set with precision, specificity and sensitivity values of 100.0, 75.0 and 95.5%, respectively. For regression, a root mean squared error of prediction (RMSEP) of 0.04 was obtained, pointing at good predictive properties. Furthermore, during mass spectrometric screening, 10 different adulterants and impurities were encountered. Using the spectral data to model the presence of each of these resulted in performant models for seven of them. All models showed promising correct-classification rates (between 92 and 96%) and good values for sensitivity, specificity and precision. For codeine and morphine, the models were not satisfactory, probably due to the low concentration of these impurities as a consequence of acetylation. For methacetin, the approach failed.

Dual Microfluidic Sensor System for Enriched Electrochemical Profiling and Identification of Illicit Drugs On-Site.

Electrochemical sensors have emerged as a new analytical tool for illicit drug detection to facilitate ultrafast and accurate identification of suspicious compounds on-site. Drugs of abuse can be identified using their unique voltammetric fingerprint at a given pH. Today, the right buffer solution is manually selected based on drug appearance, and in some cases, a consecutive analysis in two different pH solutions is required. In this work, we present a disposable microfluidic multichannel sensor system that automatically records fingerprints in two pH solutions (e.g., pH 5 and pH 12). This system has two advantages. It will overcome the manual selection of a buffer solution at the right pH, decrease analysis time, and minimize the risk of human errors. Second, the combination of two fingerprints, the superfingerprint, contains more detailed information about the samples, which enhances the selectivity of the analytical technique. First, real-time pH measurements proved that the sample can be brought to the desired pH within a minute. Subsequently, an electrochemical study on the microfluidic platform with 1 mM illicit drug standards of MDMA, cocaine, heroin, and methamphetamine showed that the characteristic voltammetric fingerprints and peak potentials are reproducible, also in the presence of common cutting agents. Finally, the microfluidic concept was validated with real confiscated samples, showing promising results for the user-friendly identification of drugs of abuse. In short, this paper presents a successful proof-of-concept study of a multichannel microfluidic sensor system to enrich the fingerprints of illicit drugs at pH 5 and pH 12, thus providing a low-cost, portable, and rapid identification system of illicit drugs with minimal user intervention.

Assessing the impact of a major electronic music festival on the consumption patterns of illicit and licit psychoactive substances in a Mediterranean city using wastewater analysis.

The consumption patterns of five categories of psychoactive substances (PS), including "conventional" illicit drugs, new psychoactive substances (NPS), therapeutic opioids, alcohol and nicotine, were studied in the city of Split, Croatia, using wastewater-based epidemiology (WBE), with an emphasis on the impact of a large electronic music festival. The study involved the analysis of 57 urinary biomarkers of PS in raw municipal wastewater samples collected in three characteristic periods, including the festival week in the peak-tourist season (July) and reference weeks in the peak-tourist season (August) and the off-tourist season (November). Such a large number of biomarkers allowed the recognition of distinct patterns of PS use associated with the festival, but also revealed some subtle differences between summer and autumn seasons. The festival week was characterized by markedly increased use of illicit stimulants (MDMA: 30-fold increase; cocaine and amphetamine: 1.7-fold increase) and alcohol (1.7-fold increase), while consumption of other common illicit drugs (cannabis and heroin), major therapeutic opioids (morphine, codeine and tramadol) and nicotine remained rather constant. Interestingly, NPS and methamphetamine clearly contributed to the festival PS signature in wastewater, but their prevalence was rather low compared to that of common illicit drugs. Estimates of cocaine and cannabis use were largely consistent with prevalence data from national surveys, whereas differences were found for typical amphetamine-type recreational drugs, particularly MDMA, and for heroin. The WBE data suggest that the largest proportion of morphine came from heroin consumption and that the percentage of heroin users seeking treatment in Split is probably rather low. The prevalence of smoking calculated in this study (30.6 %) was consistent with national survey data for 2015 (27.5-31.5 %), while the average alcohol consumption per capita >15 years (5.2 L) was lower than sales statistics suggest (8.9 L).

Strong π-Metal Interaction Enables Liquid Interfacial Nanoarray-Molecule Co-assembly for Raman Sensing of Ultratrace Fentanyl Doped in Heroin, Ketamine, Morphine, and Real Urine.

Toward the challenge on reliable determination of trace fentanyl to avoid opioid overdose death in drug crisis, here we realize rapid and direct detection of trace fentanyl in real human urine without pretreatment by a portable surface enhanced Raman spectroscopy (SERS) strategy on liquid/liquid interfacial (LLI) plasmonic arrays. It was observed that fentanyl could interact with the gold nanoparticles (GNPs) surface, facilitate the LLI self-assembly, and consequently amplify the detection sensitivity with a limit of detection (LOD) as low as 1 ng/mL in aqueous solution and 50 ng/mL spiked in urine. Furthermore, we achieve multiplex blind sample recognition and classification of ultratrace fentanyl doped in other illegal drugs, which has extremely low LODs at mass concentrations of 0.02% (2 ng in 10 µg of heroin), 0.02% (2 ng in 10 µg of ketamine), and 0.1% (10 ng in 10 µg of morphine). A logic circuit of the AND gate was constructed for automatic recognition of illegal drugs with or without fentanyl doping. The data-driven analog soft independent modeling model could quickly distinguish fentanyl-doped samples from illegal drugs with 100% specificity. Molecular dynamics (MD) simulation elucidates the underlying molecular mechanism of nanoarray-molecule co-assembly through strong π-metal interactions and the differences in the SERS signal of various drug molecules. It paves a rapid identification, quantification, and classification strategy for trace fentanyl analysis, indicating broad application prospects in response to the opioid epidemic crisis.

Which illicit drugs are injected in Oslo? A study based on analysis of drug residues in used injection equipment and self-reported information.

BACKGROUND: People who inject drugs (PWID) have a high risk of premature death due to fatal overdoses. Newly emerged fentanyls, much more potent than heroin and other opioids, may increase this risk further. Therefore, precise information on injected drugs is critical to improving prevention strategies. AIMS: This study aimed to analyse drug residues in used injection equipment in order to determine drug and drug combinations and compare and complement findings with self-reported information. METHODS: Used syringes and needles (n=766) were collected at the supervised drug consumption facilities, the needle exchange service and two low-threshold health services for problem drug users in Oslo, Norway. The material was collected every third month from June 2019 to June 2020 and analysed for 64 substances using highly specific analytical methods (ultra-high performance liquid chromatography tandem mass spectrometry). Additionally, a street-recruited sample of PWID was interviewed from 2017 to 2019 regarding their drug injection habits (n=572). RESULTS: Heroin (65.5%) or amphetamines (59.8%), often in combination (30.5%), were commonly detected in drug residues. Other opioids, stimulants or benzodiazepines were rarely detected (6.1%). Fentanyl was detected in only one syringe. Heroin was the most reported drug (77.6% during the past four weeks, 48.3% daily/almost daily), followed by amphetamines (57.5% during the past four weeks, 23.1% daily or almost daily). Injection of methadone, buprenorphine and dissolved tablets was self-reported more frequently than determined in drug residue findings. CONCLUSIONS: Analysis of the injection equipment proved useful as a non-invasive, rapid and accurate means to obtain detailed information on injected drugs in Oslo and supplement traditional PWID survey information.

Heroin and fentanyl in Dallas County: A 5-year retrospective review of toxicological, seized drug, and demographical data.

The opioid epidemic resulted in an increase in identifications of fentanyl, fentanyl analogs, and heroin, among other opioids, in the toxicology and seized drug analysis fields over the past several years. The Dallas County Southwestern Institute of Forensic Sciences, comprised of the Toxicology Laboratory and Drug Analysis Laboratory, observed a rise in fentanyl-positive analyses in both laboratories. Fentanyl positivity increased from 1.1% to 3.4% in the Toxicology Laboratory over the five years of this study, whereas 6-monoacetylmorphine (6-MAM) positivity remained relatively stable at approximately 2%. Similarly, in the Drug Analysis Laboratory, the fentanyl positivity rate changed from 0.03% to 0.60%, whereas heroin identification remained stable at approximately 8-9%. Based on data obtained from toxicology submissions, a typical fentanyl or heroin user was a white male in their late 30s. The average concentration of fentanyl in postmortem cases, antemortem cases, and 6-MAM in postmortem specimens was 9.7 ng/ml, 5.5 ng/ml, and 68.4 ng/ml, respectively. Poly-drug use was evident, with benzodiazepines being the most commonly co-administered drug with fentanyl (49.4%). Multiple drugs were identified via analysis of clandestine tablets submitted to the Drug Analysis Laboratory, including fentanyl and/or heroin in combination with compounds such as cocaine, etizolam, and acetaminophen. The most frequently identified clandestine tablet was "M367," typically manufactured to contain acetaminophen and hydrocodone, but was found to contain fentanyl or heroin. The results from this study aid in the understanding of the current opioid trends in Dallas County and provides an opportunity for comparison to other populations and geographical regions.

Evaluation of eight psychoactive drugs used in Chinese cities by wastewater-based epidemiology.

With rapid economic development, an increasing number of people suffer from mental health diseases, which are gradually receiving the attention of society. However, basic data from surveys of mental disorders are limited. Composite influent samples were collected from 26 wastewater treatment plants in 23 major cities in China. The concentrations of the psychoactive drugs diphenhydramine, fluoxetine, doxepin, imipramine, sulpiride, zolpidem, carbamazepine, and flunitrazepam in the wastewater were determined. The detection frequency of diphenhydramine, sulpiride, and carbamazepine was close to 100 %, whereas that of the compounds was lower than 35 %. Carbamazepine had the highest mean consumption (31.1 mg/d/1000 people), followed by diphenhydramine (10.4 mg/d/1000 people) and sulpiride (11.3 mg/d/1000 people). Wastewater-based epidemiology (WBE) estimates of the average use of the three drugs were lower than those from the drug statistics data. Consumption of diphenhydramine in northern China was higher than that in southern China. A correlation analysis of psychotropic and illicit drugs revealed a correlation between sulpiride and heroin use, which may be related to the adverse effects of sulpiride treatment after heroin withdrawal. Psychotropic drug use is associated with both economic and social factors. We found associations between the use of the three drugs and age, occupation, and obesity, which are risk factors for mental disorders. The results showed that the monitoring of psychotropic drug using WBE has a certain reference value for public health care and for improving the understanding of mental disorders.

Exploring the use of infrared absorption spectroscopy and two-trace two-dimensional correlation analysis for the resolution of multi-component drug mixtures.

Community drug checking provides an essential service that responds to the unpredictable and variable supply of illicit drugs. Point of care detection of trace components using portable infrared spectrometers is a harm reduction measure to prevent overdose. This study investigates the ability of weighted subtraction and two-trace two-dimensional (2T2D) correlation analysis to reveal the presence of heroin in an opioid mixture that contains heroin and fentanyl mixed with caffeine as a cutting agent. In both methods, a spectral trace was identified that provided reasonably high correlation scores to heroin when compared to entries in drug libraries. The two-trace correlation analysis produced a higher match score, suggesting that future improvements in spectral unmixing methods may enhance the reliability of detecting trace components in drugs.

6-Monoacetylmorphine-antibody distribution in tissues from heroin-related death cases: An experimental study to investigate the distributive response.

Heroin, a semisynthetic opioid drug synthesized from morphine, is the 3,6-diacetyl ester of morphine (diacetylmorphine). The post-mortem diagnosis of heroin-related death could be an issue and usually rely on a combination of investigations, including the autopsy, histological and toxicological analysis. We conducted the present study to evaluate the correlation between the heroin concentration in biological fluids (peripheral blood, bile and urine) and the post-mortem anti-6-MAM antibody expression in various tissues (brain, heart, lung, liver and kidney) using immunohistochemical staining. A quantitative analysis of the immunohistochemical reaction was carried out. 45 cases of heroin-related death investigated at the Forensic Pathology Institutes of the University of Rome, Foggia and Pisa were included. The control group was composed of 15 cases of death due to other causes, without brain lesions and negative toxicological analysis for drugs. We found a positive immunohistochemical reaction in different organs and it was related to the timing of heroin metabolization. No reaction was found in the control group. Our findings show that immunohistochemistry can be a valuable tool for the post-mortem diagnosis of acute heroin abuse. A better understanding of the timing of heroin's metabolism can be useful in the forensic field and for future therapeutic applications.

Consumption of common illicit drugs in twenty-one cities in southwest China through wastewater analysis.

Wastewater-based epidemiology (WBE) was applied to estimate illicit drugs consumption at a provincial scale in southwest China. A large-scale wastewater sampling campaign was carried out from October to November in 2021 in 156 different wastewater treatment plants (WWTPs). Two 24-h composite influent wastewater samples were collected in each WWTP. Concentrations of 11 illicit drugs or their metabolites were determined using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Benzoylecgonine, cocaine, 6-monoacetylmorphine, norketamine, 3,4-methylenedioxymethamphetamine (MDMA), and MDA were not detected in any of the wastewater samples. Methamphetamine and morphine were detected in >84% of samples, while ketamine was found in about 6% of the samples. The city-specific population-weighted consumption of methamphetamine and ketamine were in the range of 0.6-49.7 and N.D.-7.0 mg 1000 inh-1 day-1, respectively, with provincial population-weighted values of 22.6 and 2.4 mg 1000 inh-1 day-1 in southwest China. The city-specific load of morphine varied from 3.2 to 10.2 mg 1000 inh-1 day-1, with provincial population-weighted load of 6.7 mg 1000 inh-1 day-1. Taking into account therapeutic use of morphine and codeine, the provincial heroin consumption was estimated to be 10.3 mg 1000 inh-1 day-1, ranging from 1.7 to 18.5 mg 1000 inh-1 day-1 in 21 cities. Overall, the patterns of illicit drugs use were similar across southwest China, with high prevalence of methamphetamine and heroin, but relatively low use of ketamine. These findings could provide accurate drugs consumption information for timely identifying potential hotspots of illicit drugs use in southwest China.

Monitoring of changes in illicit drugs, alcohol, and nicotine consumption during Ramadan via wastewater analysis.

Illicit drug use is a global problem imposing social, economic, and health burdens on society. Wastewater-based epidemiology is an approach based on calculating the consumption of substances in the target population by analyzing the concentrations of human metabolic excretion products of licit and illicit substances in wastewater. This study estimated the changes in illicit drugs (cocaine, amphetamine, methamphetamine, ecstasy (3,4-Methylenedioxymethamphetamine), heroin, and marijuana (THC)), alcohol, and nicotine consumption in Adana Province during Ramadan compared to normal periods using wastewater-based epidemiology. An overall decrease was observed during the Ramadan Period, most strongly for ecstasy (29%) followed by heroin (19%). For cocaine, the variation was the slightest (8.6%). The differences were statistically significant for ecstasy, heroin, nicotine, and alcohol but not for cocaine, amphetamine, methamphetamine, and marijuana. This study is the first to show changes in the use of illicit drugs, alcohol, and nicotine under the influence of religious beliefs. In addition, there is limited data about illicit drugs, alcohol and nicotine abusers/users in Ramadan. This study provides information on the literature on this subject.

Illicit drug consumption estimated using wastewater analysis and compared by settlement size in New Zealand.

Estimation of consumption of illicit drugs by wastewater-based epidemiology provides estimates of community drug-use patterns. This study describes monitoring data of three illicit drugs in New Zealand using wastewater-based epidemiology. Wastewater samples were collected at monthly intervals for larger (population ~ 50,000+) cities or in smaller towns where more data was required by authorities. In other smaller towns, samples were collected every 2 months. Samples were extracted and analysed for parent compounds and metabolites of methamphetamine, MDMA, cocaine, heroin and fentanyl consumption using solid-phase extraction followed by liquid chromatography coupled with tandem-mass spectrometry (LC-MS/MS) detection. Back calculations were performed to estimate the consumption of each drug in each catchment area. Methamphetamine was the drug measured with the highest estimated mean consumption rates (724 mg/1000 people per day) in New Zealand. North Island small urban settlements had the highest estimated mean methamphetamine consumption rates (1259 mg/1000 people/day). Cocaine had the lowest estimated consumption rates (9.4 mg/1000 people/day). The highest estimated mean cocaine consumption rate was in North Island major urban settlements (24.4 mg/1000 people/day). Major urban settlements had the highest estimated mean MDMA (420 mg/1000 people/day) and cocaine consumption rates (18.8 mg/1000 people/day). South Island medium urban settlements had unexpectedly high estimated mean consumption rates of MDMA (533 mg/1000 people/day) and cocaine (17.0 mg/1000 people/day). The higher-than-expected estimated cocaine consumption was from one medium urban settlement that is also a popular tourist destination in the South Island. Heroin biomarkers were not detected at any locations, and fentanyl was detected around or below the limit of reporting. This research provides information for appropriate responses for improved social and health investment to support social services associated with illicit drug consumption.

Trace residue identification, characterization, and longitudinal monitoring of the novel synthetic opioid ß-U10, from discarded drug paraphernalia.

Empirical data regarding dynamic alterations in illicit drug supply markets in response to the COVID-19 pandemic, including the potential for introduction of novel drug substances and/or increased poly-drug combination use at the "street" level, that is, directly proximal to the point of consumption, are currently lacking. Here, a high-throughput strategy employing ambient ionization-mass spectrometry is described for the trace residue identification, characterization, and longitudinal monitoring of illicit drug substances found within >6,600 discarded drug paraphernalia (DDP) samples collected during a pilot study of an early warning system for illicit drug use in Melbourne, Australia from August 2020 to February 2021, while significant COVID-19 lockdown conditions were imposed. The utility of this approach is demonstrated for the de novo identification and structural characterization of ß-U10, a previously unreported naphthamide analog within the "U-series" of synthetic opioid drugs, including differentiation from its α-U10 isomer without need for sample preparation or chromatographic separation prior to analysis. Notably, ß-U10 was observed with 23 other drug substances, most commonly in temporally distinct clusters with heroin, etizolam, and diphenhydramine, and in a total of 182 different poly-drug combinations. Longitudinal monitoring of the number and weekly "average signal intensity" (ASI) values of identified substances, developed here as a semi-quantitative proxy indicator of changes in availability, relative purity and compositions of street level drug samples, revealed that increases in the number of identifications and ASI for ß-U10 and etizolam coincided with a 50% decrease in the number of positive detections and an order of magnitude decrease in the ASI for heroin.

Urine thebaine determination by liquid chromatography tandem mass spectrometry after poppy seed consumption.

Laboratories are challenged to distinguish whether a positive urine morphine result is due to heroin use or possible poppy seed consumption. Thebaine is an opium alkaloid that has been shown to be present in the urine of individuals who have consumed poppy seeds, as well as those who have used opium. It is not present in heroin. We present a sensitive, specific liquid chromatography tandem mass spectrometry (LC-MS/MS) assay for thebaine. We show that thebaine is detectable after consumption of two different poppy seed-containing products for up to 72 h in urine. We discuss limitations of the assay and suggest how the test might best be used.

Comparison of Illicit Drug Seizures Products of Natural Origin Using a Molecular Networking Approach.

Drug powder composition analysis is of particular interest in forensic investigations to identify illicit substance content, cutting agents and impurities. Powder profiling is difficult to implement due to multiple analytical methods requirement and remains a challenge for forensic toxicology laboratories. Furthermore, visualization tools allowing seizure products identification appear to be under-used to date. The aim of this study is to present the utility of molecular networking for the composition establishment of natural origin drugs. A powder suspected to contain heroin and three powders suspected to contain cocaine obtained from law enforcement agency seizures were analyzed using untargeted screening by liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS/MS). Molecular networking and metabolite annotation applied to suspected heroin sample allowed rapid confirmation of its illicit content (heroin), the identification of structurally related major impurities (6-monoacetylmorphine, 6-monoacetylcodeine, noscapine, and papaverine), as well as cutting agents (acetaminophen and caffeine). The cocaine powder profiling allowed the comparison of its constituents in a semi-quantitative manner (cocaine, benzoylecgonine, trans/cis-cinnamoylcocaine, trimethoxycocaine, hexanoylecgonine methylester, caffeine, hydroxyzine, levamisole, and phenacetin), bringing additional information for their identification, including geographically sourcing of natural product and their putative place in the supply chain. Although this approach does not replace the profiling techniques used by forensic laboratories, the use of molecular networks provides a visual overview of structurally related constituents which aids the comparison and investigation of seizure powders. Molecular networks offers here an ideal way to depict structurally related and unrelated compounds in these often complex mixtures of chemicals.

Carbon and nitrogen isotopic analysis of morphine from opium and heroin samples originating in the four major heroin producing regions.

The forensic analysis of stable isotopes is a valuable tool to geo-source natural or semisynthetic drugs such as cocaine and heroin. The present study describes a novel methodology to isolate morphine from opium for isotopic analysis. Furthermore, this isotopic data from regional sources is corroborated with morphine data obtained from seized heroin (deacetylated to morphine) from the same regions. All five primary alkaloids of opium, namely, morphine, codeine, thebaine, noscapine, and papaverine, were quantified using high performance liquid chromatography with photodiode array (PDA) detector before the preparative experiment to gather a complete major alkaloidal profile. Morphine fractions of authentic opium submissions from Mexico, South America, Southwest Asia, and Southeast Asia were isolated and collected using preparative high performance liquid chromatography, and the collected morphine samples were subsequently analyzed by isotope ratio mass spectrometry. Carbon and nitrogen isotope data are presented. The data demonstrate that nitrogen ratios are capable of differentiating samples from Mexico and South America while carbon ratios are able to distinguish Southwest Asian samples from other source regions. Analogous results have routinely been observed (as part of Heroin Signature Program analysis) for morphine obtained from deacetylated authentic heroin samples from the same source regions. The results suggest that the poppy growing region has a greater influence on the carbon and nitrogen isotope values than the heroin manufacturing processes employed. When utilized in conjunction with existing signature methodologies, carbon and nitrogen isotope ratio data can enhance the ability to geo-source heroin.

Findings of illicit drugs in hair of children at different ages.

Hair is a preferred material to detect exposure or use of illegal drugs in children. In the present study, we investigated a total of 387 hair samples for commonly applied illegal drugs of children up to 16 years. Analysis was by liquid chromatography/mass spectrometry with LOQs of 0.01 ng/mg hair for all analytes except tetrahydrocannabinol carboxylic acid with an LOQ of 0.1 pg/mg hair. Results were firstly compared with our in-house statics on results from adults' hair, and secondly to literature data. We started from the assumption that drug concentrations decrease with increasing age.Results were assigned to 4 different age groups (< 1 year, 1-< 6 years, 6-< 14 years, 14-16 years). As expected, higher results were obtained in age groups 1 and 2. The lowest concentrations were present in age group 3, whereas an increase could be observed in group 4 except heroin. In babies, positive results may be due to in utero exposure, breast milk feeding, and a close physical contact. All drugs under investigation such as cannabinoids, cocaine, amphetamines, and opiates have been detected in breast milk as well as in skin excretions such as sebum, sweat and cutaneous cells. For most drugs, average concentrations in children hair were lower than in adult hair when compared with our in-house statistics. Interestingly, the increase of cannabinoids, cocaine, and amphetamines concentrations in adolescents' hair points to a deliberate use of these drugs possibly in addition to passive exposure. This observation shows that age groups 1 and 4 are most vulnerable if caregivers or parents are drug users, even if the sources of positive drug findings differ.

Detection of trace drugs of abuse in baby formula using solid-phase microextraction direct analysis in real-time mass spectrometry (SPME-DART-MS).

The intentional or unintentional adulteration of baby formula with drugs of abuse is one of the many increasingly complex samples forensic chemists may have to analyze. This sample type presents a challenge because of a complex matrix that can mask the detection of trace drug residues. To enable screening of baby formula for trace levels of drugs, the use of solid-phase microextraction (SPME) coupled with direct analysis in real-time mass spectrometry (DART-MS) was investigated. A suite of five drugs was used as adulterants and spiked into baby formula. Samples were then extracted using SPME fibers which were analyzed by DART-MS. Development of a proof-of-concept method was completed by investigating the effects of the DART gas stream temperature and the linear speed of the sample holder. Optimal values of 350°C and 0.2 mm/s were found. Once the method was established, representative responses and sensitivities for the five drugs were measured and found to be in the range of single ng/mL to hundreds ng/mL. Additional studies found that the presence of the baby formula matrix increased analyte signal (relative to methanolic solutions) by greater than 200%. Comparison of the SPME-DART-MS method to a traditional DART-MS method for trace drug detection found at least a factor of 13 improvement in signal for the drugs investigated. This work demonstrates that SPME-DART-MS is a viable technique for the screening of complex matrices, such as baby formula, for trace drug residues and that development of a comprehensive method is warranted.

An unusual detection of tert-butyl-4-anilinopiperidine-1-carboxylate in seizures of falsified 'Xanax' tablets and in items in a suspected heroin seizure submitted by Irish law enforcement.

The identification of tert-butyl-4-anilinopiperidine-1-carboxylate (4-anilinopiperdine-t-BOC or 4-AP-t-BOC) in many seized falsified 'Xanax' tablets has been reported after being encountered in forensic casework in late 2019 and early 2020 in Ireland. This substance was also detected in a pink powder submitted for analysis in March 2020. The pink powder was part of a larger seizure comprising brown powders which contained morphine or diamorphine (heroin) or a type of counterfeit heroin or heroin adulterant (known as 'bash'). Novel benzodiazepines and other substances are being detected as ingredients in falsified benzodiazepine tablets more frequently on the illicit market. The detection of 4-AP-t-BOC in benzodiazepine tablets is noteworthy and 4-AP-t-BOC is added to the list of adulterants found in benzodiazepine tablets emerging in Europe. The presence of 4-AP-t-BOC in both falsified 'Xanax' and powdered seizures is unusual, and analytical data are presented to assist with the identification of this compound in suspected illicit substances. The presence of 4-AP-t-BOC in the tablets was confirmed using gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry analyses, and spectral fragmentation pathways were suggested. To the authors' best knowledge, information about the biological activity of 4-AP-t-BOC is not available. The removal of the t-BOC protecting group yields 4-anilinopiperidine which has been reported to be involved in the synthesis of fentanyl.

Aerodynamic Thermal Breakup Droplet Ionization in Mass Spectrometric Drug Analysis.

Aerodynamic thermal breakup droplet ionization (ATBDI) in mass spectrometric drug analysis is considered. Cocaine, heroin, and the main alkaloids of opium (morphine, codeine, papaverine) were chosen as the test compounds. The principles of ATBDI ionization are discussed. The dependences of the intensities of the peaks of the target compounds on temperature during ATBDI ionization are also considered. In some cases, a comparison of ATBDI ionization with electrospray ionization (ESI) was performed. In addition, a comparison of methods is demonstrated by the analysis of confiscated opium that was provided by the local police department. Five major alkaloids are found in opium: morphine, codeine, thebaine, papaverine, and narcotine.