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

Abstract

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.

A fatal case involving the highest ever reported 4‐CMC concentration

“…These values are noticeably lower than in the described case, which could result from a dose (20 g) what was taken, which is significantly higher than the usual recreationally used ones (tens or hundreds of milligrams). A worth‐noticing fact is that all of the cases described in literature included combined intoxications with other substances, for example U‐47700 [12], 25B‐NBOMe [10], THC, MDMA, amphetamine, and diazepam [9], N‐ethylpentylone [3], as well as amphetamine and ethyl alcohol [11]. In most of the mentioned cases, 4‐CMC was not the main substance detected, which outstands the here described case as a poisoning by a single substance, additionally in such a high concentration.…”

“…The concentration presented in here described case exceeds this value by more than 4.5 times. In other papers describing 4-CMC intoxications the following concentrations of 4-CMC in blood were determined: 0.181-75.3 ng/ml (nonfatal cases [9][10][11]) and 0.6-698 ng/ml (fatal cases [3,12]). These values are noticeably lower than in the described case, which could result from a dose (20 g) what was taken, which is significantly higher than the usual recreationally used ones (tens or hundreds of milligrams).…”

“…These values are noticeably lower than in the described case, which could result from a dose (20 g) what was taken, which is significantly higher than the usual recreationally used ones (tens or hundreds of milligrams). A worth-noticing fact is that all of the cases described in literature included combined intoxications with other substances, for example U-47700 [12], 25B-NBOMe [10],…”

Quantification and distribution of 4-fluoroisobutyryl fentanyl (4-FiBF) in postmortem biological samples using UHPLC–QqQ-MS/MS

“…Our results suggest that the However, in the case of co-administered cathinone analogs (4-CMC and N-ethylpentylone), the differences were not as significant. Nevertheless, taking into account the coincidence of 4-FiBF with cathinones (which are unstable in blood samples [21,[23][24][25]), and the high concentrations of 4-FiBF in the liver, it is appropriate to collect the fragment of this tissue together with blood samples for further toxicological studies. The elimination of 4-FiBF occurs rapidly, and the urinary concentrations are extremely high.…”

A review of synthetic cathinones emerging in recent years (2019–2022)

“…Additionally, N-ethylhexedrone has neurotoxic properties and is toxic to microglia [128]. There are numerous descriptions in the literature of fatal [97,127,[129][130][131][132][133] and nonfatal [100,127,[134][135][136] poisoning cases where N-ethylhexedrone has been detected in biological material (Table 1). The blood concentrations detected in fatal and non-fatal cases were in the ranges of 4-285 ng/mL and 1-84 ng/mL, respectively, and the poisoning effects described included symptoms typical of sympathomimetic and serotonergic toxidromes.…”