Quantification of U-47700 and its metabolites: N-desmethyl-U-47700 and N,N-didesmethyl-U-47700 in 12 autopsy blood samples employing SPE/LC–ESI-MS-MS

Abstract

Purpose The paper presents a report on the comprehensive assessment of a novel synthetic opioid (NSO) termed U-47700, and its two metabolites: N-desmethyl-U-47700 and N,N-didesmethyl-U-47700 in autopsy blood samples taken from 12 cases of fatal poisonings. Methods The analysis of the examined samples was based on the solid-phase extraction/liquid chromatography-electrospray ionization-tandem mass spectrometry method, which was developed in the validation process. In the quantitative analytical studies, deuterium analytes analogs were used, namely U-47700-d 6 and N-desmethyl-U-47700-d 3 .Results The validation parameters of the method were determined, including the limits of quantification on the 1 ng/mL level, calibration curves range of 1-1000 ng/ml, intra-assay precisions and accuracies of 1.1-20.2% and −18.9-9%, respectively, and inter-assay precisions and accuracies of 2.9-13.0% and -11.4-3.3%, respectively. The matrix effects and the extraction efficiencies were formed at the levels of 54.0-119% and 53.0-118%, respectively. The parent substance and its metabolites in blood samples have been shown to be relatively stable under various conditions within the 21-day study. The concentration levels demonstrated in the analyzed blood samples were: U-47700 in the range of 83-24,000 ng/mL, N-desmethyl-U-47700 in the range of 2.0-7520 ng/mL and N,N-didesmethyl-U-47700 in the range of 18-1947 ng/mL. Conclusions The simultaneous quantification of U-47700, N-desmethyl-U-47700 and N,N-didesmethyl-U-47700 seems very useful to confirm the cause of death and to estimate antemortem interval. To our knowledge this is the first trial to measure phase I metabolites of U-47700 in authentic human blood samples.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Toxic lifespan of the synthetic opioid U-47,700 in Finland verified by re-analysis of UPLC-TOF-MS data

“…According to the background information, in most cases the deceased had a history of drug abuse. The concentrations detected in these 10 cases were similar to those reported by Mohr et al [6], Rojek et al [14] and Smith et al [15] who found median U-47,700 Among the studied cases, there was one case in which no other psychoactive substances, besides U-47,700, were detected (Case 4, Table 1). The blood concentration of U-47,700 in this case (0.27 mg/L) did not significantly differ from the median U-47,700 concentration.…”

“…1), a highly selective m-receptor agonist originally developed by the company Upjohn in 1970s [3]. Since 2016, several reports have been published on serious adverse effects associated with U-47,700, including death cases [4][5][6][7][8][9][10][11][12][13][14][15].…”

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

“…The substance was found to be stable in all conditions. The stability of U-47700 was also confirmed by Rojek et al [7], whose fortified blood with U-47700 and its metabolites (N-desmethyl U-47700, N,N-didesmethyl U-47700) at low concentrations (25 ng/mL) and stored it at − 30 °C, + 3 °C, and + 20 °C. The analyses were performed after 1, 7, 14, and 21 days of storage.…”

“…Substances from this group pose a threat to public health in many countries, especially in Europe and the USA [2]. U-47700 has been already detected in, e.g., Belgium (2016) [3], where in 2017 it was involved in 5 deaths [4], as well as in Finland (10 deaths in 2016 and 2017) [5], Italy (2017) [6], Poland [7], the United Kingdom Supplementary Information The online version contains supplementary material available at https ://doi.org/10.1007/s1141 9-020-00568 -1.…”

“…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].…”