Postmortem concentrations of the synthetic opioid U-47700 in 26 fatalities associated with the drug

Fels, Helena; Lottner-Nau, Stefanie; Sax, Tanja; Roider, Gabriele; Graw, Matthias; Auwärter, Volker; Mußhoff, Frank

doi:10.1016/j.forsciint.2019.04.010

Cited by 39 publications

(33 citation statements)

References 20 publications

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“…Besides fentanyl, many other synthetic opioids of more recent synthesis have appeared on the market: the racemic form of MT-45, one of the first designer opioids to achieve some degree of popularity with an in vitro and in vivo potency similar to morphine [ 211 , 212 ], its newly identified fluorinated analogue 2F-MT-45 [ 213 ], the highly potent and efficient isotonitazene [ 214 ], U-47700 and AH-7921 that caused numerous fatal and non-fatal intoxications [ 215 , 216 , 217 ], U-50488 and furanyl fentanyl that are frequently encountered in postmortem caseworks [ 218 ], U-51754, U-47931E, and methoxyacetylfentanyl [ 219 ].…”

Section: Synthetic Opioidsmentioning

confidence: 99%

Sex and Gender Differences in the Effects of Novel Psychoactive Substances

et al. 2020

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Sex and gender deeply affect the subjective effects and pharmaco-toxicological responses to drugs. Men are more likely than women to use almost all types of illicit drugs and to present to emergency departments for serious or fatal intoxications. However, women are just as likely as men to develop substance use disorders, and may be more susceptible to craving and relapse. Clinical and preclinical studies have shown important differences between males and females after administration of “classic” drugs of abuse (e.g., Δ9-tetrahydrocannabinol (THC), morphine, cocaine). This scenario has become enormously complicated in the last decade with the overbearing appearance of the new psychoactive substances (NPS) that have emerged as alternatives to regulated drugs. To date, more than 900 NPS have been identified, and can be catalogued in different pharmacological categories including synthetic cannabinoids, synthetic stimulants (cathinones and amphetamine-like), hallucinogenic phenethylamines, synthetic opioids (fentanyls and non-fentanyls), new benzodiazepines and dissociative anesthetics (i.e., methoxetamine and phencyclidine-derivatives). This work collects the little knowledge reached so far on the effects of NPS in male and female animal and human subjects, highlighting how much sex and gender differences in the effects of NPS has yet to be studied and understood.

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Section: Synthetic Opioidsmentioning

confidence: 99%

Sex and Gender Differences in the Effects of Novel Psychoactive Substances

et al. 2020

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“…207,208 Intoxication with synthetic opioids has been associated with noncardiogenic pulmonary oedema, acute lung injury, diffuse alveolar haemorrhage and rhabdomyolysis. 209,210 Withdrawal from synthetic opioids may present with physiological and psychological distress. 211 Statistics on morbidity and mortality may not reflect the real-life situation as users may recover, for example, from a mixed heroin/synthetic opioid overdose when naloxone is administered and the illicit drug documented will then be heroin and not a synthetic one.…”

Section: Synthetic Opioidsmentioning

confidence: 99%

New psychoactive substances: a review and updates

Shafi

Berry

Sumnall

et al. 2020

Therapeutic Advances in Psychopharmacology

173

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New psychoactive substances (NPS) are a heterogeneous group of substances. They are associated with a number of health and social harms on an individual and societal level. NPS toxicity and dependence syndromes are recognised in primary care, emergency departments, psychiatric inpatient and community care settings. One pragmatic classification system is to divide NPS into one of four groups: synthetic stimulants, synthetic cannabinoids, synthetic hallucinogens and synthetic depressants (which include synthetic opioids and benzodiazepines). We review these four classes of NPS, including their chemical structures, mechanism of action, modes of use, intended intoxicant effects, and their associated physical and mental health harms. The current challenges faced by laboratory testing for NPS are also explored, in the context of the diverse range of NPS currently available, rate of production and emergence of new substances, the different formulations, and methods of acquisition and distribution.

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“…According to the European Drug Report 2018 [14] in 2016, 4-CMC was the second most frequently confiscated cathinone in Europe and the one seized in the largest amounts (890 kg). The literature contains cases of deaths related to the use of synthetic cathinones, individually or in combination with substances from other groups [7,[15][16][17][18][19][20].…”

Section: Introductionmentioning

confidence: 99%

Fatal intoxication with U-47700 in combination with other NPS (N-ethylhexedrone, adinazolam, 4-CIC, 4-CMC) confirmed by identification and quantification in autopsy specimens and evidences

2021

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Purpose We present a case of fatal intoxication with U-47700 in combination with other NPS (N-ethylhexedrone, adinazolam, 4-chloro-N-isopropylcathinone (4-CIC), 4-chloromethcathinone (4-CMC) and sertraline) confirmed by identification and quantification in biological materials and evidences found at the scene in 2017 in Poland. Methods Blood and urine samples were extracted with ethyl acetate from alkaline medium (pH 9); powders/crystals were diluted with methanol. The analysis was carried out using ultra-high-performance liquid chromatography–tandem mass spectrometry. Validation criteria were evaluated for blood and urine at the concentrations of 10 and 100 ng/mL. Results The validation parameters of the method were within acceptable ranges. In the presented case, the determined concentrations of drugs were as follows, in blood: U-47700, 1470 ng/mL; N-ethylhexedrone, 58 ng/mL; adinazolam, 18 ng/mL; 4-CIC, 8.0 ng/mL; 4-CMC, 1.7 ng/mL; in urine: U-47700, 3940 ng/mL; N-ethylhexedrone, 147 ng/mL; adinazolam, 82 ng/mL; 4-CIC, 130 ng/mL; 4-CMC, 417 ng/mL. Sertraline (blood, 89 ng/mL; urine, 32 ng/mL) was also determined in both materials. The same substances were also found in 5 powders/crystals: U-47700 (12% by weight), N-ethylhexedrone (54%), adinazolam (14%), 4-CIC (23%), 4-CMC (26%). After 775 days of storage, biological samples at + 4 °C, the most stable substance was sertraline and the less, synthetic cathinones, especially 4-CIC and 4-CMC. Conclusions The described case of fatal intoxication with NPS presented postmortem concentrations of U-47700, 4-CMC, N-ethylhexedrone, adinazolam and 4-CIC for the first time in the literature. The paper also showed stability study of these substances stored at + 4 °C for 775 days.

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Postmortem concentrations of the synthetic opioid U-47700 in 26 fatalities associated with the drug

Cited by 39 publications

References 20 publications

Sex and Gender Differences in the Effects of Novel Psychoactive Substances

Sex and Gender Differences in the Effects of Novel Psychoactive Substances

New psychoactive substances: a review and updates

Fatal intoxication with U-47700 in combination with other NPS (N-ethylhexedrone, adinazolam, 4-CIC, 4-CMC) confirmed by identification and quantification in autopsy specimens and evidences

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