Monitoring illicit pentobarbital availability in the United States: A National Drug Early Warning System briefing.

BACKGROUND: Pentobarbital is a Schedule II/III short-acting barbiturate with limited medical use in humans. Veterinary professionals use pentobarbital to euthanize dogs, cats, and other companion animals. Pentobarbital is also utilized in capital punishment and small amounts are illegally shipped or diverted to assist in suicides. However, five kilograms of pentobarbital smuggled in from Mexico was recently seized by an organized crime drug enforcement task force (along with fentanyl, heroin, and cocaine), which may suggest a shift in illicit supply. We investigated potential indicators of illicit pentobarbital use or availability in the US to help determine whether this drug is becoming an emerging public health concern. METHODS: The National Drug Early Warning System requested information on pentobarbital from its sentinel surveillance sites and collaborators and conducted a search of current literature. RESULTS: In early 2024, multiple batches of counterfeit pills (e.g., pressed as "M30s" to represent oxycodone) confiscated near the Southwest border tested positive for pentobarbital plus combinations of fentanyl, fentanyl analogs, and xylazine. Other indicators suggest pentobarbital is being smuggled in powder form and possibly sold as another drug such as heroin. One national drug analysis program detected pentobarbital in 217 drug submissions from 2020 to 2023, and there were at least 12 fatal exposures linked to use from 2020 to 2022. CONCLUSION: Continued monitoring of illicit use and availability is needed as pentobarbital may continue to appear on the illicit market. Unknown exposure can occur if the drug is mixed into counterfeit pills or sold in powder form represented to be another drug.

Application of terahertz Time-Domain spectroscopy and chemometrics-based whale optimization algorithm in PDE5 inhibitor detection.

Combating the illicit use of PDE5 inhibitor drugs is a focal point in forensic science research. In order to achieve rapid identification of such drugs, this study applies terahertz time-domain spectroscopy combined with chemometrics to establish a fast and accurate detection method for PDE5 inhibitors. The optimal detection method is determined by comparing the spectral performance of three optical parameters, namely absorption coefficient, refractive index, and dielectric constant. Linear discriminant models based on different spectral parameters, whale optimization algorithm optimized extreme learning machine models, and whale optimization algorithm optimized random forest models are established. The effectiveness and performance of principal component analysis and competitive adaptive reweighted sampling algorithm for spectral feature data selection are also investigated. The PDE5 inhibitor identification model based on the competitive adaptive reweighted sampling - whale optimization algorithm - random forest (CARS-WOA-RF) model achieves an accuracy of 98.61%, and the identification model for two concentrations of Sildenafil achieves 100% accuracy. The results demonstrate that terahertz time-domain spectroscopy combined with chemometrics can effectively detect various common types of PDE5 inhibitor drugs and different concentrations.

Amphetamine-type Stimulants: Novel Insights into their Actions and use Patterns.

This review focuses on the effects and mechanisms of action of amphetamine-type stimulants (ATS) and their adverse effects on the cardiovascular, nervous, and immune systems. ATS include amphetamine (AMPH), methamphetamine (METH, "crystalmeth," or "ice"), methylenedioxymethamphetamine (MDMA, "ecstasy," or "Molly"), MDMA derivatives (e.g., methylenedioxyamphetamine [MDA] and methylenedioxy-N-ethylamphetamine [MDEA]), khat, and synthetic cathinones. The first section of this paper presents an overview of the historical aspects of ATS use, their initial clinical use, and regulations. The second part reviews the acute and chronic impact and the most salient clinical effects of ATS on the central nervous and cardiovascular systems, skin, and mouth. The chemical structure, pharmacokinetics, and classic and non-canonical pharmacological actions are covered in the third section, briefly explaining the mechanisms involved. In addition, the interactions of ATS with the central and peripheral immune systems are reviewed. The last section presents data about the syndemic of ATS and opioid use in the North American region, focusing on the increasing adulteration of METH with fentanyl.

Amphetamine-type Stimulants: Novel Insights into their Actions and use Patterns

ABSTRACT This review focuses on the effects and mechanisms of action of amphetamine-type stimulants (ATS) and their adverse effects on the cardiovascular, nervous, and immune systems. ATS include amphetamine (AMPH), methamphetamine (METH, "crystalmeth," or "ice"), methylenedioxymethamphetamine (MDMA, "ecstasy," or "Molly"), MDMA derivatives (e.g., methylenedioxyamphetamine [MDA] and methylenedioxy-N-ethylamphetamine [MDEA]), khat, and synthetic cathinones. The first section of this paper presents an overview of the historical aspects of ATS use, their initial clinical use, and regulations. The second part reviews the acute and chronic impact and the most salient clinical effects of ATS on the central nervous and cardiovascular systems, skin, and mouth. The chemical structure, pharmacokinetics, and classic and non-canonical pharmacological actions are covered in the third section, briefly explaining the mechanisms involved. In addition, the interactions of ATS with the central and peripheral immune systems are reviewed. The last section presents data about the syndemic of ATS and opioid use in the North American region, focusing on the increasing adulteration of METH with fentanyl.

New psychoactive substances and low-income countries: a burgeoning (and neglected) crisis.

Abstract: New psychoactive substances (NPS) are compounds intended to replicate the effects of legal and illegal drugs. The continuous detec-tion of new NPS via several forensic toxicology techniques attests to the considerable NPS popularity all over the world, although such determinations rely on still indecisive findings, given the elusiveness inherent in NPS and the the lack of standardized and uniformly applied detection and screening techniques. A worrisome and neglected issue is the proliferation of NPS and other drugs of abuse in developing countries. Demographics may partly explain such an emerging threat, which in a globalized world is likely to have an impact that goes well beyond national borders, especially in light of the criminal organiza-tions' ability to function and operate in the cyberspace, harnessing the potential of the "dark web" to overstep the boundaries and oversight mechanisms put in place by nations and international institutions.

Pharmacists' perceptions and attitudes toward drug importation into the State of Florida.

BACKGROUND: The Department of Health and Human Services and the Food and Drug Administration released the Safe Importation Action Plan in July 2020 detailing methods to import medicines from Canada to combat increasing drug costs. In November 2020, Florida became the first state in the United States to create and propose an importation plan from Canada. This study examines the proposal submitted by Florida, Florida pharmacists' perceptions of the program on patient safety, and Florida pharmacists' thoughts on the pharmacy operational impact. METHODS: This was a cross-sectional study utilizing an electronic questionnaire sent to pharmacist members of the Florida Pharmacy Association. The survey incorporated closed-ended and open-ended questions. The results from the study were reported and analyzed through descriptive statistics, qualitative and quantitative data. RESULTS: Two-hundred and forty-four pharmacists responded to the survey. Of those respondents, 25% stated they had no knowledge about Florida's drug importation plan. Less than 12% of respondents stated they would trust the safety and quality of imported medicines. Seventy percent of pharmacists expressed concerns regarding the changes required in pharmacy operations to increase medicine safety. About half of the respondents questioned whether this plan would promote cost-savings as intended. CONCLUSION: Florida pharmacists believe the drug importation plan does not address all aspects of patient and medicine safety and expressed concerns regarding logistical operations of a pharmacy. This article highlights those concerns and acts as a summons to action.

Comparison of different methods used in drugs of abuse for sample validity testing including pH methods, specific gravity methods, TECO™ Drug Adulteration Test Strip and oxidant assay.

Objectives: In the absence of sample validity testing, a healthcare provider may fail to identify a patient's adulteration of their urine sample. This study compared different methods for specific gravity (SG), pH, TECO™ Drug Adulteration Test Strip (dipstick) and oxidant assay to explain the differences and also make an informative decision on method selection. Methods: Creatinine, SG and pH measurements are essential in sample validity testing. SG and pH automated chemical methods are compared against pH meter method, SG refractometer and dipstick method. Also, oxidant assay was compared against dipstick method. Results: SG chemical method agreement with refractometer is 81.9% and with dipstick method is 64.7%. The refractometer method agreement with dipstick method is 66.1%. pH chemical method agreement with pH Meter method is 74.3% and with dipstick method is 81.4%. pH meter method agreement is 85.7% with dipstick method. Results were analysed using Deming regression analysis and F-test. SG chemical method correlated better with refractometer than the dipstick method. Oxidant assay correlated well with dipstick method in detecting adulterants such as pyridinium chlorochromate, nitrite and bleach. Conclusions: Varying degrees of differences were seen in the SG and pH measurements. These differences were both method and instrument dependent. The automated chemical methods are recommended alongside oxidant assay for consistency, accuracy and faster turn-around time as part of sample validity testing for drugs of abuse.

Determination of cocaine adulterants in human urine by dispersive liquid-liquid microextraction and high-performance liquid chromatography.

This study aimed to determine simultaneously five major street cocaine adulterants (caffeine, lidocaine, phenacetin, diltiazem, and hydroxyzine) in human urine by dispersive liquid-liquid microextraction (DLLME) and high-performance liquid chromatography. The chromatographic separation was obtained in gradient elution mode using methanol:water plus trifluoroacetic acid 0.15% (v/v) (pH = 1.9) at 1 mL min-1 as mobile phase, at 25 °C, detection at 235 nm, and analysis time of 20 min. The effect of major DLLME operating parameters on extraction efficiency was explored using the multifactorial experimental design approach. The optimum extraction condition was set as 4 mL human urine sample alkalized with 0.5 M sodium phosphate buffer (pH 12), NaCl (15%, m/v), 300 µL acetonitrile (dispersive solvent), and 800 µL chloroform (extraction solvent). Linear response (r2 ≥ 0.99) was obtained in the range of 180-1500 ng mL-1 with suitable selectivity, quantification limit (180 ng mL-1), mean recoveries (33.43-76.63%), and showing relative standard deviation and error (within and between-day assays) ≤15%. The analytes were stable after a freeze-thaw cycle and a short-term room temperature stability test. This method was successfully applied in real samples of cocaine users, suggesting that our study may contribute to the appropriate treatment of cocaine dependence or with the cases of cocaine acute intoxication.

Drug adulteration of food supplements: A threat to public health in the European Union?

Food supplements have been playing an increasingly important role in the consumers' awareness nowadays. They are widespread and - according to popular belief - healthier and safer than synthetic drugs. In the European Union (EU) food supplements are classified as foodstuffs and thus not subjected to any specific safety assessments prior to commercialisation. With the growing popularity of food supplements, there is an increased need for more effective control of their production and distribution. The aim of this study was to examine the food notifications, recorded since 2003 via the EU RASFF database with particular regard to recent years, as well as to evaluate the involvement of different EU state structures in the fight against drug-adulterated food supplements with regard to efficacy and safety. In recent years, the number of RASFF notifications in the category of dietetic foods, food supplements and fortified foods, especially related to unauthorised composition, has increased significantly. The majority of EU Member States authorities, who responded to the study, consider drug-adulterated food supplements to be a public health threat. However, the competences of different official structures within the Member States concerning such products do not appear to be clearly defined. Regulators should thus think of stricter legislative solutions to increase the safety of public health.

Adulteration of proprietary Chinese medicines and health products with undeclared drugs: experience of a tertiary toxicology laboratory in Hong Kong.

AIMS: Proprietary Chinese medicines (pCMs) and health products, generally believed to be natural and safe, are gaining popularity worldwide. However, the safety of pCMs and health products has been severely compromised by the practice of adulteration. The current study aimed to examine the problem of adulteration of pCMs and health products in Hong Kong. METHODS: The present study was conducted in a tertiary referral clinical toxicology laboratory in Hong Kong. All cases involving the use of pCMs or health products, which were subsequently confirmed to contain undeclared adulterants, from 2005 to 2015 were reviewed retrospectively. RESULTS: A total of 404 cases involving the use of 487 adulterated pCMs or health products with a total of 1234 adulterants were identified. The adulterants consisted of approved drugs, banned drugs, drug analogues and animal thyroid tissue. The six most common categories of adulterants detected were nonsteroidal anti-inflammatory drugs (17.7%), anorectics (15.3%), corticosteroids (13.8%), diuretics and laxatives (11.4%), oral antidiabetic agents (10.0%) and erectile dysfunction drugs (6.0%). Sibutramine was the most common adulterant (n = 155). The reported sources of these illicit products included over-the-counter drug stores, the internet and Chinese medicine practitioners. A significant proportion of patients (65.1%) had adverse effects attributable to these illicit products, including 14 severe and two fatal cases. Psychosis, iatrogenic Cushing syndrome and hypoglycaemia were the three most frequently encountered adverse effects. CONCLUSIONS: Adulteration of pCMs and health products with undeclared drugs poses severe health hazards. Public education and effective regulatory measures are essential to address the problem.

Dispersive liquid-liquid microextraction based on solidification of floating organic drop and high-performance liquid chromatography to the analysis of cocaine's major adulterants in human urine.

A simple method has been proposed for the determination of cocaine's major adulterants (caffeine, levamisole, lidocaine, phenacetin, diltiazem, and hydroxyzine) in human urine by dispersive liquid-liquid microextraction based on solidification of floating organic drop (DLLME-SFO) in combination with high-performance liquid chromatography - photodiode array detector (HPLC-PDA). The reversed-phase chromatographic separation was obtained with a column C18 extended (250×4.6mm; 5µm; 80Å) in gradient elution mode using acetonitrile-trifluoroacetic acid 0.026% (v,v) (pH=2.5) at 1mLmin-1 as mobile phase, at 25°C, and detection at 235nm. The analysis time was 25min. This condition had the best resolution factors (>1.15), retention factors (>0.68), number of plates (>2094.9), and separation factors (>1.05) for all targets, indicating a good separation. The kind of extraction and dispersive solvent were investigated for unifactorial design. The buffer pH, the volume of extraction and disperser solvent, and the amount of salt were optimized for full factorial design. Under optimum conditions, human urine samples were alkalized with 0.5M sodium phosphate buffer (pH 10) and added to sodium chloride (20%m/v). Acetonitrile (150µL) and 1-dodecanol (30µL) were used as dispersive and extraction solvent, respectively. The method presented linear range of 312.5-3125ngmL-1 to caffeine and levamisole and 187.5-1875ngmL-1 to lidocaine, phenacetin, diltiazem, and hydroxyzine. The limit of quantification was 187.5ngmL-1 to lidocaine, phenacetin, diltiazem, and hydroxyzine and 312.5ngmL-1 for caffeine and levamisole. The recovery mean values were between 6.0 and 42.6%. The method showed good precision and accuracy, with within- and between-run relative standard deviation and relative error less than 15%. The samples were stable after freeze-thaw cycle and short-term room temperature stability tests. Besides, this method was satisfactorily applied in urine of cocaine users. It is expected that this method, which was the first to combine the use of DLLME-SFO and HPLC-PDA for the determination of cocaine's major adulterants in human urine, will contribute to the accuracy in the diagnosis of acute intoxication, the proper planning of therapeutic measures, as well as to the favorable prognostic of cocaine intoxicated patients.

Use of diffusion-ordered NMR spectroscopy and HPLC-UV-SPE-NMR to identify undeclared synthetic drugs in medicines illegally sold as phytotherapies.

The informal (and/or illegal) e-commerce of pharmaceutical formulations causes problems that governmental health agencies find hard to control, one of which concerns formulas sold as natural products. The purpose of this work was to explore the advantages and limitations of DOSY and HPLC-UV-SPE-NMR. These techniques were used to identify the components of a formula illegally marketed in Brazil as an herbal medicine possessing anti-inflammatory and analgesic properties. DOSY was able to detect the major components present at higher concentrations. Complete characterization was achieved using HPLC-UV-SPE-NMR, and 1D and 2D NMR analyses enabled the identification of known synthetic drugs. These were ranitidine and a mixture of orphenadrine citrate, piroxicam, and dexamethasone, which are co-formulated in a remedy called Rheumazim that is used to relieve severe pain, but it is prohibited in Brazil because of a lack of sufficient pharmacokinetic and pharmacodynamic information.