The occurrence of non-anatomical therapeutic chemical-international nonproprietary name molecules in suspected illegal or illegally traded health products in Europe: A retrospective and prospective study.

The General European Official Medicines Control Laboratory (OMCL) Network (GEON), co-ordinated by the European Directorate for the Quality of Medicines & HealthCare (EDQM), regularly organises market surveillance studies on specific categories of suspected illegal or illegally traded products. These studies are generally based on a combination of retrospective and prospective data collection over a defined period of time. This paper reports the results of the most recent study in this context with the focus on health products containing non-Anatomical Therapeutic Chemical-International Nonproprietary Name (ATC-INN) molecules. In total 1104 cases were reported by 16 countries for the period between January 2017 and the end of September 2019. The vast majority of these samples (83%) were collected from the illegal market, while only 3% originated from a legal source. For the rest of the samples, categorisation was not possible. Moreover, 69% of all the reported samples were presented as medicines, including sexual performance enhancers, sports performance enhancers, physical performance enhancers and cognitive enhancers or nootropic molecules that act on the central nervous system (CNS). Although the popularity of anabolics, PDE-5 inhibitors and CNS drugs in illegal products has already been reported, the study showed some new trends and challenges. Indeed, 11% of the samples contained molecules of biological origin, that is, research peptides, representing the second most reported category in this study. Furthermore, the study also clearly shows the increasing popularity of Selective Androgen Receptor Modulators and nootropics, two categories that need attention and should be further monitored.

Investigation of drug products received for analysis in the Swedish STRIDA project on new psychoactive substances.

The web-based open sale of unregulated new psychoactive substances (NPS) has shown a steady increase in recent years. Analysis of drug products sold as NPS is useful to confirm the true chemical contents, for comparison with the substances detected in corresponding body fluids, but also to study drug trends. This work describes the examination of 251 drug products that were randomly submitted for analysis in 173 cases of suspected NPS-related intoxications in the Swedish STRIDA project in 2010-2015. Of the products, 39% were powders/crystals, 32% tablets/capsules, 16% herbal materials, 8% liquids, 1% blotters, and 4% others. The analysis involved tandem mass spectrometry and nuclear magnetic resonance spectroscopy. In 88 products (35%), classic psychoactive substances, prescription pharmaceuticals, dietary supplements, or doping agents were found; however, in none of these cases had an NPS-related intoxication been indicated from product markings or patient self-reports. Another 12 products tested negative for psychoactive substances. The remaining 151 products contained 86 different NPS (30% contained ≥2 substances). In 104 drug products, a specific NPS ingredient was indicated based on labelling (69%) or patient self-report; in 92 cases this was also analytically confirmed to be correct. Overall, the NPS products submitted for analysis in the STRIDA project showed a high degree of consistency between suspected and actual content (88%). The results of related urine and/or blood analysis further demonstrated that the patients commonly (89%) tested positive for the indicated NPS, but also revealed that polysubstance intoxication was common (83%), indicating use of additional drug products.

Opioid intoxications involving butyrfentanyl, 4-fluorobutyrfentanyl, and fentanyl from the Swedish STRIDA project.

BACKGROUND: The supply of unregulated "new psychoactive substances" (NPS) has shown a steady increase over the past six years. This report from the Swedish STRIDA project describes analytically confirmed non-fatal intoxications involving butyrfentanyl (butyrylfentanyl) or 4-fluorobutyrfentanyl (para-fluorobutyrfentanyl), two fentanyl analogues recently introduced as NPS opioids. STUDY DESIGN: Observational case series of consecutive patients with suspected acute NPS exposure and requiring hospital care from all over Sweden. PATIENTS AND METHODS: From May 2014 to January 2015, blood and urine samples were obtained from four intoxication cases involving butyrfentanyl and one case involving 4-fluorobutyrfentanyl (men, 19-30 years) presenting in emergency departments (ED) or intensive care units (ICU). Laboratory analysis of serum and/or urine samples was performed by multi-component liquid chromatography-mass spectrometry methods. Data on clinical features were collected during consultations with the Poisons Information Centre and retrieved from medical records. CASE DETAILS: Of the five patients, two were discharged home from the ED and three were admitted to the ICU, of whom two required intubation and mechanical ventilation. Clinical features included typical opioid symptoms such as unconsciousness, respiratory depression, and apnea. In one case, naloxone successfully countered the effects. All patients were discharged the same or the following day. Butyrfentanyl was detected in two serum (0.6 and 0.9 ng/mL) and three urine (2.0-65.6 ng/mL) samples from three of four cases; three cases also contained fentanyl. In the 4-fluorobutyrfentanyl case, the substance was detected in serum (∼15 ng/mL) and urine (∼10 ng/mL). In four cases, other NPS and/or classical drugs were also detected. Analysis of two "butyrfentanyl" NPS products (nasal spray and powder) brought to hospital by patients showed that the 10-fold more potent fentanyl was the main active ingredient (∼7.5-10-fold higher amount) in both. CONCLUSION: Typical and potentially life-threatening opioid toxicity was seen in acute intoxications involving butyrfentanyl, 4F-butyrfentanyl, and fentanyl. The incorrect labelling of butyrfentanyl NPS products which instead mainly contained fentanyl is alarming, given the narrow range between a safe and a lethal dose for opioids.