Xylazine: A Drug Adulterant of Clinical Concern.

PURPOSE OF REVIEW: The opioid epidemic has been responsible for significant morbidity and mortality in the USA and worldwide. As a result, it is essential to recognize the threat these potent drugs can cause when illicitly used. Specifically, introducing fentanyl as a drug adulterant has been shown to impact overdose rates drastically. In this regard, the Drug Enforcement Agency recently released a public safety alert announcing the new threat of a new adulterant called xylazine. Xylazine is a powerful animal sedative with a different mechanism of action when compared to illicit opioids such as heroin and fentanyl. Xylazine is typically injected intravenously via a syringe, often in combination with multiple other drugs. One of the most common drugs, xylazine, is taken in combination with fentanyl, with users of this drug combination describing xylazine as prolonging the euphoric sensation produced by fentanyl. RECENT FINDINGS: Xylazine may cause adverse effects such as bradycardia, brief hypertension followed by hypotension, premature ventricular contractions, ataxia, slurred speech, sedation, and respiratory depression. Much of the recent literature on xylazine use in humans comes from case reports and review articles. Related to widespread use in veterinary medicine and increasing circulation in illicit drug markets, there is a critical need for public awareness and additional clinical-based studies to further increase understanding of mediated or modulated pharmacological effects of xylazine in humans. Further research is urgently needed to more clearly understand the implications of unregulated xylazine in the illicit drug market, to formulate public health interventions, and to implement harm reduction strategies.

Understanding the barriers and facilitators to implementing and sustaining Mobile Overdose Response Services from the perspective of Canadian key interest groups: a qualitative study.

INTRODUCTION: Unregulated supply of fentanyl and adulterants continues to drive the overdose crisis. Mobile Overdose Response Services (MORS) are novel technologies that offer virtual supervised consumption to minimize the risk of fatal overdose for those who are unable to access other forms of harm reduction. However, as newly implemented services, they are also faced with numerous limitations. The aim of this study was to examine the facilitators and barriers to the adoption of MORS in Canada. METHODS: A total of 64 semi-structured interviews were conducted between November 2021 and April 2022. Participants consisted of people who use substances (PWUS), family members of PWUS, health care professionals, harm reduction workers, MORS operators, and members of the general public. Inductive thematic analysis was used to identify the major themes and subthemes. RESULTS: Respondents revealed that MORS facilitated a safe, anonymous, and nonjudgmental environment for PWUS to seek harm reduction and other necessary support. It also created a new sense of purpose for operators to positively contribute to the community. Further advertising and promotional efforts were deemed important to increase its awareness. However, barriers to MORS implementation included concerns regarding privacy/confidentiality, uncertainty of funding, and compassion fatigue among the operators. CONCLUSION: Although MORS were generally viewed as a useful addition to the currently existing harm reduction services, it's important to monitor and tackle these barriers by engaging the perspectives of key interest groups.

Aflatoxin M1 Concentrations, Adulterants, Microbial Loads, and Physicochemical Properties of Raw Milk Collected From Nekemte City, Ethiopia.

Milk is an essential part of the human diet and is a nutrient-rich food that improves nutrition and food security. The aim of this study was to determine the presence and concentration of aflatoxin M1 (AFM1), adulterants, microbial loads, and physicochemical properties of raw cow's milk (CM) in Nekemte City, Ethiopia. A total of 12 samples of fresh CM were purposefully collected from four kebeles in the city (Bake Jama, Burka Jato, Cheleleki, and Bakanisa Kese) based on the potential of each milk production and distributor site. The AFM1 concentration was determined by high-performance liquid chromatography (HPLC) with a Sigma-Aldrich standard (St. Louis, MO, USA). The concentrations of AFM1 in Bake Jama, Burka Jato, Cheleleki, and Bakanisa Kese were found to be 0.01-0.03 g/L, 0.31-0.35 g/L, 0.19-0.21 g/L, and 0.04-0.07 g/L, respectively. The concentrations of AFM1 in the present study varied significantly (p < 0.05) and ranged from 0.01 g/L to 0.35 g/L. These results show that of the 12 samples tested, all were positive for AFM1 and contaminated to varying degrees. The results of this study also revealed that the concentration of AFM1 in 7 (58%) of the 12 milk samples was above the European Union's (EU) maximum tolerance limit (0.05 g/L). The present study also revealed that of the investigated adulterants, only the addition of water had positive effects on three milk samples, while the remaining adulterants were not detected in any of the milk samples. The total bacterial count (TBC) and total coliform count (TCC) were significantly (p < 0.05) different and ranged from 5.53 to 6.82 log10cfumL-1 and from 4.21 to 4.74 log10cfumL-1, respectively. The physicochemical properties of the milk samples in the present study were significantly (p < 0.05) different and ranged from 2.8% to 5.75% fat, 7.03% to 9.75% solid-not-fat (SNF), 2.35% to 3.61% protein, 3.33% to 5.15% lactose, 11.54% to 13.69% total solid, 0.16% to 0.18% titratable acid, 26.7 to 32.1°C, 6.35 to 6.55 pH, and 1.027 to 1.030 specific gravity. The physicochemical parameters of the raw milk in the study area met the required quality standards. Hence, further studies are required to determine the extent of the problem and the factors associated with high levels of AFM1 in raw milk in the study areas, including the detection of aflatoxin B1 (AFB1) in animal feed.

Molecular Aspects of the Interactions between Selected Benzodiazepines and Common Adulterants/Diluents: Forensic Application of Theoretical Chemistry Methods.

Benzodiazepines are frequently encountered in crime scenes, often mixed with adulterants and diluents, complicating their analysis. This study investigates the interactions between two benzodiazepines, lorazepam (LOR) and alprazolam (ALP), with common adulterants/diluents (paracetamol, caffeine, glucose, and lactose) using infrared (IR) spectroscopy and quantum chemical methods. The crystallographic structures of LOR and ALP were optimized using several functionals (B3LYP, B3LYP-D3BJ, B3PW91, CAM-B3LYP, M05-2X, and M06-2X) combined with the 6-311++G(d,p) basis set. M05-2X was the most accurate when comparing experimental and theoretical bond lengths and angles. Vibrational and 13C NMR spectra were calculated to validate the functional's applicability. The differences between LOR's experimental and theoretical IR spectra were attributed to intramolecular interactions between LOR monomers, examined through density functional theory (DFT) optimization and quantum theory of atoms in molecules (QTAIM) analysis. Molecular dynamics simulations modeled benzodiazepine-adulterant/diluent systems, predicting the most stable structures, which were further analyzed using QTAIM. The strongest interactions and their effects on IR spectra were identified. Comparisons between experimental and theoretical spectra confirmed spectral changes due to interactions. This study demonstrates the potential of quantum chemical methods in analyzing complex mixtures, elucidating spectral changes, and assessing the structural stability of benzodiazepines in forensic samples.

Untargeted Metabolomics Based on Ultra-High-Performance Liquid Chromatography Coupled with Quadrupole Orbitrap High-Resolution Mass Spectrometry for Differential Metabolite Analysis of Pinelliae Rhizoma and Its Adulterants.

The present study investigates the chemical composition variances among Pinelliae Rhizoma, a widely used Chinese herbal medicine, and its common adulterants including Typhonium flagelliforme, Arisaema erubescens, and Pinellia pedatisecta. Utilizing the non-targeted metabolomics technique of employing UHPLC-Q-Orbitrap HRMS, this research aims to comprehensively delineate the metabolic profiles of Pinelliae Rhizoma and its adulterants. Multivariate statistical methods including PCA and OPLS-DA are employed for the identification of differential metabolites. Volcano plot analysis is utilized to discern upregulated and downregulated compounds. KEGG pathway analysis is conducted to elucidate the differences in metabolic pathways associated with these compounds, and significant pathway enrichment analysis is performed. A total of 769 compounds are identified through metabolomics analysis, with alkaloids being predominant, followed by lipids and lipid molecules. Significant differential metabolites were screened out based on VIP > 1 and p-value < 0.05 criteria, followed by KEGG enrichment analysis of these differential metabolites. Differential metabolites between Pinelliae Rhizoma and Typhonium flagelliforme, as well as between Pinelliae Rhizoma and Pinellia pedatisecta, are significantly enriched in the biosynthesis of amino acids and protein digestion and absorption pathways. Differential metabolites between Pinelliae Rhizoma and Arisaema erubescens are mainly enriched in tyrosine metabolism and phenylalanine metabolism pathways. These findings aim to provide valuable data support and theoretical references for further research on the pharmacological substances, resource development and utilization, and quality control of Pinelliae Rhizoma.

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.

[Quality identification of Aurantii Fructus Immaturus from different origins and their adulterants].

Aurantii Fructus Immaturus(AFI) is a traditional Chinese herbal medicine with multiple origins from Citrus aurantium and its legally cultivated variants. With advancements in agricultural biotechnology, many new cultivated varieties have sprung up,leading to an abundance of AFI adulterants and chaos in the herbal medicine markets. This study developed a specific identification method for AFI and its closely related adulterants by examining the appearance trait, content of extract, and multiple ingredients,involving indicators such as the ratio of pulp capsule to cross section diameter(Pc/Cs ratio), the content of extract, and the profile of 11 ingredients. The research finds that:(1) Pc/Cs ratio can conveniently identify adulterants such as Poncirus trifoliata, Ju, and Babagan from the genuine AFI.(2) The extract content can be used to identify adulterants originated from C. wilsonii with C. aurantium.(3) The contents of synephrine in all the samples were in accordance with the Chinese Pharmacopoeia except for the adulterants from P. trifoliata, C. wilsonii, C. aurantium 'Changshanhuyou' and orah mandarins. The synephrine content was high as 1. 40% in some C. sinensis varieties. The mass fraction of hesperidin was over 10. 00% in C. sinensis, while it was below 2. 50% in C. aurantium. C. aurantium contained high levels of naringin(3. 96%-15. 21%) and neo-hesperidin(9. 38%-21. 93%).(4) The compositions of adulterants from P. trifoliata and C. wilsonii were more similar to that of C. aurantium 'Daidai', but with significantly lower neo-hesperidin content(0. 03%-0. 14%) than that in C. aurantium, and they lacked hesperetin and tangeretin. C. maxima(originating from C. maxima) showed closer composition to Choucheng and hybrid originated from Citrus aurantium × Poncirus trifoliata, but had higher hesperidin content(3. 13%) than that in C. aurantium. Ju was closely related to C. sinensis and neither contained naringin nor neo-hesperidin. Hesperidins in Babagan and orah mandarins were similar to that in C. sinensis, with none containing rhoifolin. These quality indicators in combination can accurately distinguish between C. sinensis, C. aurantium, and their closely related adulterants(P. trifoliata, C. wilsonii, C. maxima, orah mandarins and C. reticulata), which are expected to provide a systematic method for quality control of AFI.

Development of a thin layer chromatography-based method to detect sorbitol presence in milk and its applicability in formalin preserved milk samples.

Sorbitol has been the new and emerging adulterant in dairy industry. The main aim of the study was to develop a method to detect sorbitol in milk, which is not affected by other sugars, polyols and formalin. Hence, a thin layer chromatographic (TLC) method was standardized to detect the sorbitol in milk. In the study 90 s duration for the impregnation of Silica gel 60F TLC plates with Cu- ions was found suitable to resolve sorbitol as a distinct spot. The standardized conditions were (1) developing solvent system consisting of n-propanol: ethyl acetate: water (7:1:2), (2) 0.5% of potassium permanganate in 0.1 M NaOH as color developing reagent. (3) Drying temperature (65°C/ 10 min.) after spraying the color developing reagent. The limit of detection was 0.2% of added sorbitol in milk. The standardized method could also detect the sorbitol in the presence of sucrose, glucose and polyols like mannitol and maltitol. In both cow and buffalo milk samples the standardized methodology performed well in detection of sorbitol. The method also performed well in sorbitol spiked formalin preserved milk samples. This method can be an alternative to the other methods involving costly equipment in detecting adulteration of milk with sorbitol.

Current strategies to guarantee the authenticity of coffee.

As they become more health conscious, consumers are paying increasing attention to food quality and safety. In coffee production, fraudulent strategies to reduce costs and maximize profits include mixing beans from two species of different economic value, the addition of other substances and/or foods, and mislabeling. Therefore, testing for coffee authenticity and detecting adulterants is required for value assessment and consumer protection. Here we provide an overview of the chromatography, spectroscopy, and single-nucleotide polymorphism-based methods used to distinguish between the major coffee species Arabica and Robusta. This review also describes the techniques applied to trace the geographical origin of coffee, based mainly on the chemical composition of the beans, an approach that can discriminate between coffee-growing regions on a continental or more local level. Finally, the analytical techniques used to detect coffee adulteration with other foods and/or coffee by-products are discussed, with a look at the practice of adding pharmacologically active compounds to coffee, and their harmful effects on health.

Detection of botanical adulterants in saffron powder.

Saffron is a unique spice obtained by drying stigmas of saffron flowers (Crocus sativus L.). Due to its high price, economically motivated adulteration occurs relatively often. The presented study aimed to develop an effective strategy for the detection of the following potential botanical adulterants used for a saffron substitution or dilution: safflower (Carthamus tinctorius L.), calendula (Calendula officinalis L.), turmeric (Curcuma longa L.), achiote (Bixa orellana L.), red pepper (Capsicum spp.), mountain arnica (Arnica montana L.), beet (Beta vulgaris L.), and pomegranate (Punica granatum L.). A non-target screening strategy based on ultra-high performance reverse-phase liquid chromatography coupled to tandem high-resolution mass spectrometry (UHPLC-HRMS/MS) was employed for the analysis of an aqueous ethanol plant extract. By using multivariate statistical methods, principal components analysis (PCA), and partial least squares discriminant analysis (PLS-DA), for processing the generated "chemical fingerprints," metabolites unique to the investigated plants could be identified. To enable routine saffron authenticity control by target screening, an internal spectral database was developed; currently, it involves 82 unique markers. In this way, the detection addition as low as 1% (w/w) of all analyzed botanical adulterants in admixture with saffron was possible. The developed method was used to control 7 saffron powder samples from the Czech market, and none of the monitored adulterants were confirmed.

Exploring customers' perceptions of food adulteration at bazaars and supermarkets in Dhaka, Bangladesh; a qualitative exploration.

BACKGROUND: Food adulteration is an increasingly recognized global public health problem. In low- and middle-income countries like Bangladesh, adulteration is difficult to detect and respond to. We explored customers' perceptions on food adulteration, perception of risk and connections between information, participant characteristics and patterns of adulterated food concerns that impact risk perception in urban Bangladesh. METHODS: A formative study was conducted in Dhaka, between June and August 2015 at a supermarket and a wet market. We explored community awareness and response to chemical contaminants (adulterants) among participants from a range of socio-economic backgrounds. The team conducted 38 in-depth interviews with 12 customers and 4 staff from a supermarket, and 12 customers and 10 vendors from a wet market. Participants were selected purposively. Audio recorded data were coded based on thematic content and analyzed manually. RESULTS: We asked participants how common foods were likely adulterated, and most gave figures of 70% or more. They reported that foods were adulterated with chemicals or artificial colors, especially fish, milk, and vegetables. The supermarket more commonly sold packaged foods with nutritional and expiry information on the label; and offered convenience in terms of building size, layout, and cleanliness. All customers from the wet market thought that foods were cheaper and fresher than from supermarkets. Supermarket customers expressed greater concern about adulterated foods than wet market customers. Most participants from both markets reported that food adulteration is invisible, adulterated foods cannot be avoided, and have long-term negative health impacts including cancer, diabetes, paralysis, heart attack, and others. Nearly half of customers from both markets were concerned about the poor nutritional value of adulterated food. Participants from both settings expressed the need for access to credible information about adulteration to help choose safe foods. The majority expressed the need for government action against those who are responsible for adulteration. CONCLUSIONS: Food adulteration was considered a major health threat. The government could act on food adulteration prevention if provided credible population-based data on disease burden, a model food sampling and testing protocol, a model for inspections, organizational strengthening and training, example social and behavioral change communications with estimated costs.

First drug-checking study at an electronic festival and fentanyl detection in the central region of Mexico.

BACKGROUND: Perception of drug adulteration has increased in Mexico, but there is little research on adulterants and toxicity. The aim of this study was to identify drug composition in an electronic music outdoor festival nearby Mexico City. METHODS: The participants completed a questionnaire with demographic data, harm reduction strategies, drug-use patterns, history, and the drug they expected to find. We took a small sample of each substance and prepared it for drug checking. A two-section drug testing station was placed within the grounds of the festival. Interaction with participants occurred at the front part. Drug checking was conducted at the rear part. The service was free of charge, voluntary and confidential. Forty persons aged 22 to 48 years participated (mode = 28), of which 92.5% were male, most (82.5%) were single. Through the Substance Analysis Program of "ReverdeSer Collective," we conducted the testing with the attendants that provided 51 drug samples, following ethical and biosafety protocols. We used colorimetry, Fourier Transform Infrared Spectroscopy, and fentanyl immunoassay strips for sample analysis. RESULTS: Substances of choice among attendants were psychostimulants (MDMA and other amphetamine-like drugs) and hallucinogens. Most samples contained what the users expected plus adulterants. Main adulterants were methylene-dioxy-ethyl-amphetamine, methylene-dioxy-propyl-amphetamine, hydroxyamphetamine, and the selective serotonin reuptake inhibitor venlafaxine. Fentanyl was present in 2 out of 4 cocaine samples and in 14 of the 22 confirmed MDMA samples. CONCLUSIONS: Some of the adulterants found pose serious health risks, especially fentanyl, amphetamine-like substances, and venlafaxine. Therefore, it is urgent to monitor these adulterants at electronic music festivals and to implement prevention, treatment, and harm reduction public policies. Naloxone distribution and drug-assisted therapies should be part of government programs in Mexico.

Evaluating Technologies to Identify Fentanyl and Adulterants in Street Drug Paraphernalia: Qualitative Perspectives of Service Providers and Their Clientele.

Background: Opioid overdose deaths continue to present major public health challenges in the U.S. Harm reduction agencies have begun using drug checking technologies to identify adulterants in the local drug supply and reduce overdose risk among people who use drugs (PWUD). Through qualitative and ethnographic methods, we assess the use of portable mass spectrometers at a harm reduction agency in a Northeastern U.S. city. Methods: We conducted participant observation, and on-the-spot qualitative interviews with harm-reduction staff members (n = 10) and their clientele (n = 17) between May 2019 and December 2020. Interviews explored emic views on drug checking (process, logistics, technology), and perceived benefits and challenges. We used thematic content analysis techniques to code and analyze interview transcriptions. Results: Implementation and use of drug checking devices were not free of challenges and malfunctions, often delaying drug checking opportunities and increasing suspicions and distrust among clients. Yet, staff members perceived that when working properly, or in conjunction with an additional device, they offered information about purchased drugs that could empower clients and potentially lead to positive behavior change. Use of these devices also enhanced engagement between harm reduction staff and PWUD, facilitating meaningful conversations around self-advocacy and harm reduction engagement. Conclusion: We report qualitative findings on the experiences and perceptions of drug checking devices among harm reduction staff and PWUD. Our findings indicate that use of this technology has the potential to decrease risk behaviors, expand health promotion services, and help reduce high rates of fentanyl-related overdose.

Determination of Phosphodiesterase Type-5 Inhibitors (PDE-5) in Dietary Supplements.

This study proposed a high-performance thin-layer chromatography (HPTLC) screening method to detect phosphodiesterase 5 (PDE-5) inhibitors as possible adulterant agents in various dietary supplements. Chromatographic analysis was performed on silica gel 60F254 plates using a mixture of ethyl acetate:toluene:methanol:ammonia in a volume ratio of 50:30:20:0.5 as a mobile phase. The system provided compact spots and symmetrical peaks of sildenafil and tadalafil with retardation factor values of 0.55 and 0.90, respectively. The analysis of products purchased from the internet or specialized stores demonstrated the presence of sildenafil, tadalafil, or both compounds in 73.3% of products, highlighting inadequacies and inconsistencies in the labeling, as all dietary supplements were declared to be natural. The results were confirmed using ultra-high-performance liquid chromatography coupled with a positive electrospray ionization high-resolution tandem mass spectrometry (UHPLC-HRMS-MS) method. Furthermore, in some samples, vardenafil and various analogs of PDE-5 inhibitors were detected using a non-target HRMS-MS approach. The results of the quantitative analysis revealed similar findings between the two methods, with adulterant quantities found to be similar to or higher than those in approved medicinal products. This study demonstrated that the HPTLC method is a suitable and economical method for screening PDE-5 inhibitors as adulterants in dietary supplements intended for sexual activity enhancement.

Molecular Insights and Clinical Outcomes of Drugs of Abuse Adulteration: New Trends and New Psychoactive Substances.

Adulteration is a well-known practice of drug manufacturers at different stages of drug production. The intentional addition of active ingredients to adulterate the primary drug may enhance or mask pharmacological effects or may produce more potent drugs to increase the number of available doses and the dealer's profit. Adulterants found in different drugs change over time in response to different factors. A systematic literature search in PubMed and Scopus databases and official international organizations' websites according to PRISMA guidelines was performed. A total of 724 studies were initially screened, with 145 articles from PubMed and 462 from Scopus excluded according to the criteria described in the Method Section. The remaining 117 records were further assessed for eligibility to exclude articles without sufficient data. Finally, 79 studies were classified as "non-biological" (n = 35) or "biological" (n = 35 case reports; n = 9 case series) according to the samples investigated. Although the seized samples analyses revealed the presence of well-established adulterants such as levamisole for cocaine or paracetamol/acetaminophen for heroin, the reported data disclosed new adulteration practices, such as the use of NPS as cutting agents for classic drugs of abuse and other NPS. For example, heroin adulterated with synthetic cannabinoids or cocaine adulterated with fentanyl/fentalogues raised particular concern. Notably, adulterants play a role in some adverse effects commonly associated with the primary drug, such as levamisole-adulterated cocaine that may induce vasculitis via an autoimmune process. It is essential to constantly monitor adulterants due to their changing availability that may threaten drug consumers' health.

Development of the Volatile Fingerprint of Qu Aurantii Fructus by HS-GC-IMS.

Volatile components are important active ingredients of Rutaceae. In this study, HS-GC-IMS (headspace-gas chromatography-ion mobility spectrometry) was used to study the volatile compounds of Qu Aurantii Fructus, and a total of 174 peaks were detected, 102 volatile organic compounds (131 peaks) were identified. To compare the volatile compounds of Qu Aurantii Fructus with its similar medical herb, Aurantii Fructus, and their common adulterants, principal component analysis (PCA) and cluster analysis (CA) were performed based on the signal intensity of all the detected peaks. The results showed that Qu Aurantii Fructus and Aurantii Fructus (Citrus aurantium L.) were clustered into one group, while their common adulterants could be well distinguished in a relatively independent space. In order to distinguish Qu Aurantii Fructus from Aurantii Fructus, the peaks other than the average intensity ±2 standard deviation (95% confidence interval) were taken as the characteristic components by using the Gallery Plot plug-in software. Additionally, the fingerprint method was established based on the characteristic compounds, which can be used to distinguish among Qu Aurantii Fructus, Aurantii Fructus and their common adulterants quickly and effectively. We found that the characteristic components with higher content of Qu Aurantii Fructus were nerol, decanal, coumarin and linalool. This study provides a novel method for rapid and effective identification of Qu Aurantii Fructus and a new dimension to recognize the relationship between Qu Aurantii Fructus and Aurantii Fructus.

Xylazine detected in unregulated opioids and drug administration equipment in Toronto, Canada: clinical and social implications.

BACKGROUND: The North American opioid overdose crisis is driven in large part by the presence of unknown psychoactive adulterants in the dynamic, unregulated drug supply. We herein report the first detection of the psychoactive veterinary compound xylazine in Toronto, the largest urban center in Canada, by the city's drug checking service. METHODS: Toronto's Drug Checking Service launched in October 2019. Between then and February 2021, 2263 samples were submitted for analysis. The service is offered voluntarily at harm reduction agencies that include supervised consumption services. Samples were analyzed using gas chromatography-mass spectrometry or liquid chromatography-high resolution mass spectrometry. Targeted and/or untargeted screens for psychoactive substances were undertaken. RESULTS: In September 2020, xylazine was first detected by Toronto's Drug Checking Service. Among samples analyzed from September 2020 to February 2021 expected to contain fentanyl in isolation (610) or in combination with methamphetamine (16), xylazine was detected in 46 samples (7.2% and 12.5% of samples, respectively). Samples were predominantly drawn from used drug equipment. Three of the samples containing xylazine (6.5%) were associated with an overdose. CONCLUSION: We present the first detection of xylazine in Toronto, North America's fourth-largest metropolitan area. The increased risk of overdose associated with use of xylazine and its detection within our setting highlights the importance of drug checking services in supporting rapid responses to the emergence of potentially harmful adulterants. These data also highlight the clinical challenges presented by the dynamic nature of unregulated drug markets and the concomitant need to establish regulatory structures to reduce their contribution to overdose morbidity and mortality.

Applications of Raman spectroscopic techniques for quality and safety evaluation of milk: A review of recent developments.

Milk is a complete nutrient source for humans. The quality and safety of milk are critical for both producers and consumers, thereby the dairy industry requires rapid and nondestructive methods to ensure milk quality and safety. However, conventional methods are time-consuming and laborious, and require complicated preparation procedures. Therefore, the exploration of new milk analytical methods is essential. This current review introduces the principles of Raman spectroscopy and presents recent advances since 2012 of Raman spectroscopic techniques mainly involving surface-enhanced Raman spectroscopy (SERS), fourier-transform (FT) Raman spectroscopy, near-infrared (NIR) Raman spectroscopy, and micro-Raman spectroscopy for milk analysis including milk compositions, microorganisms and antibiotic residues in milk, as well as milk adulterants. Additionally, some challenges and future outlooks are proposed. The current review shows that Raman spectroscopic techniques have the promising potential for providing rapid and nondestructive detection of milk parameters. However, the application of Raman spectroscopy on milk analysis is not common yet since some limitations of Raman spectroscopy need to be overcome before making it a routine tool for the dairy industry.

A hierarchical screening method for detection of illegal adulterants in Fur seal ginseng pills by profiling analysis of HPLC multi-dimensional fingerprints.

A novel method for hierarchical screening of illegal adulterants in Fur seal ginseng pills products was developed by multi-dimensional fingerprint profiling analysis. Fingerprint feature of the samples was acquired by high-performance liquid chromatography analysis of 11 batches of samples with diode array detector and fluorescence detector, and then potential illegal adulterants including phosphodiesterase type-5 inhibitors, androgens, α receptor antagonists and yohimbine, were further separated at multiple wavelengths to reduce or remove interferences from sample matrix for highlight their chromatographic characteristics. Accordingly, a hierarchical screening strategy was designed by first-order and second-order fingerprints combined with spectral examination to achieve high accuracy and reliability. The method was successfully applied to screening of illegal adulterants in real samples, and it also exhibited good quantification performance through validation tests. From 16 batches of samples, three suspected samples were confirmed to be positive, containing 9.37µg/g of testosterone, 18.8 µg/g of tadalafil, and 48.5 µg/g of sildenafil, respectively. The recoveries and relative standard deviations were in the range of 83.6-103.1% and 4.2-6.8%, respectively. The proposed method provided a simple, efficient and promising alternative to monitoring functional foods.

A new approach to ion exchange chromatography with conductivity detection for adulterants investigation in dietary supplements.

The extent of adulteration of dietary supplements has significantly increased in recent years. This situation worries health authorities and requires auxiliary analytical tools for the investigation of illegal substances purposely added. Ion exchange chromatography with conductivity detection is a consolidated analytical technique for the determination of inorganic compounds in various matrices. This technique has been applied to the pharmaceutical characterization of mainly impurities and degradation products. This work presents a new approach to ion exchange chromatography as a screening method to investigate the presence of amfepramone, femproporex, sibutramine, bisacodyl and amiloride in dietary supplements advertised for weight loss. The method was optimized and validated using a Metrosep C4 100/4.0 cation exchange column. The mobile phase consisted of 1.8 mm HNO3 containing 2% acetonitrile (v/v), with a flow rate of 0.9 ml min-1 , and nonsuppressed conductivity detection was applied. The limits of detection and quantification varied from 1.01 to 3.62 mg L-1 and from 1.48 to 8.72 mg L-1 , respectively. The proposed method was successful applied to 78 solid dietary supplement samples, in two of which adulterations were found. Moreover, ion exchange chromatography with conductivity detection could be easily used for quality control without prior complex sample pre-treatment.