Abstract
Purpose: The detection of a novel psychoactive substance, 2F-MT-45, a fluorinated analogue of the synthetic opioid MT-45, was reported in a single seized tablet. MT-45, 2F-, 3F- and 4F-MT-45 were synthesised and reference analytical data were reported. The in vitro and in vivo metabolisms of MT-45 and 2F-MT-45 were investigated. Method: The reference standards and seized sample were characterised using nuclear magnetic resonance spectroscopy, ultra-performance liquid chromatography–quadrupole time of flight mass spectrometry, gas chromatography–mass spectrometry, attenuated total reflectance-Fourier transform infrared spectroscopy and Raman spectroscopy. Presumptive tests were performed and physicochemical properties of the compounds determined. Metabolite identification studies using human liver microsomes, human hepatocytes, mouse hepatocytes and in vivo testing using mice were performed and identified MT-45 metabolites were confirmed in authentic human urine samples. Results: Metabolic pathways identified for MT-45 and 2F-MT-45 were N-dealkylation, hydroxylation and subsequent glucuronidation. The major MT-45 metabolites identified in human in vitro studies and in authenticated human urine were phase I metabolites and should be incorporated as analytical targets to existing toxicological screening methods. Phase II glucuronidated metabolites were present in much lower proportions. Conclusions: 2F-MT-45 has been detected in a seized tablet for the first time. The metabolite identification data provide useful urinary metabolite targets for forensic and clinical testing for MT-45 and allows screening of urine for 2F-MT-45 and its major metabolites to determine its prevalence in case work.
| Original language | English |
|---|---|
| Pages (from-to) | 359-374 |
| Number of pages | 16 |
| Journal | Forensic Toxicology |
| Volume | 36 |
| Issue number | 2 |
| Early online date | 5 Apr 2018 |
| DOIs | |
| Publication status | Published - Jul 2018 |
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Keywords
- Novel psychoactive substances
- MT-45
- 2F-MT-45
- Metabolite profiles
- Forensic Toxicology
- Clinical Toxicology
- Synthetic Opioids
- analytical chemistry
Cite this
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Chemical synthesis, characterisation and in vitro and in vivo metabolism of the synthetic opioid MT-45 and it's newly identified fluorinated analogue 2F-MT-45 with metabolite confirmation in urine samples from known drug users. / McKenzie, Craig (Lead / Corresponding author); Sutcliffe, Oliver B. (Lead / Corresponding author); Read, Kevin; Scullion, Stanley; Epemolu, Rafiu; Fletcher, Daniel; Helander, Anders; Beck, Olof; Rylski, Alexia; Antonides, Lysbeth; Riley, Jennifer; Smith, Shannah; Nic Daeid, Niamh.
In: Forensic Toxicology, Vol. 36, No. 2, 07.2018, p. 359-374.Research output: Contribution to journal › Article
TY - JOUR
T1 - Chemical synthesis, characterisation and in vitro and in vivo metabolism of the synthetic opioid MT-45 and it's newly identified fluorinated analogue 2F-MT-45 with metabolite confirmation in urine samples from known drug users
AU - McKenzie, Craig
AU - Sutcliffe, Oliver B.
AU - Read, Kevin
AU - Scullion, Stanley
AU - Epemolu, Rafiu
AU - Fletcher, Daniel
AU - Helander, Anders
AU - Beck, Olof
AU - Rylski, Alexia
AU - Antonides, Lysbeth
AU - Riley, Jennifer
AU - Smith, Shannah
AU - Nic Daeid, Niamh
N1 - S.A. Smith is funded by the Engineering and Physical Sciences Research Council (EPSRC) Doctoral Training Programme. The authors acknowledge the work of L. Ellis of the Drug Discovery Unit, University of Dundee for Physico-Chemical analysis and Y. Shishikura, F. Simeons, L. Ferguson, E. Pinto and L. Stojanovski also of the Drug Discovery Unit, University of Dundee; and S. Ward for presumptive testing. S. Ward was funded by a Royal Society of Chemistry Analytical Chemistry Trust Fund Internship Grant.
PY - 2018/7
Y1 - 2018/7
N2 - Purpose: The detection of a novel psychoactive substance, 2F-MT-45, a fluorinated analogue of the synthetic opioid MT-45, was reported in a single seized tablet. MT-45, 2F-, 3F- and 4F-MT-45 were synthesised and reference analytical data were reported. The in vitro and in vivo metabolisms of MT-45 and 2F-MT-45 were investigated. Method: The reference standards and seized sample were characterised using nuclear magnetic resonance spectroscopy, ultra-performance liquid chromatography–quadrupole time of flight mass spectrometry, gas chromatography–mass spectrometry, attenuated total reflectance-Fourier transform infrared spectroscopy and Raman spectroscopy. Presumptive tests were performed and physicochemical properties of the compounds determined. Metabolite identification studies using human liver microsomes, human hepatocytes, mouse hepatocytes and in vivo testing using mice were performed and identified MT-45 metabolites were confirmed in authentic human urine samples. Results: Metabolic pathways identified for MT-45 and 2F-MT-45 were N-dealkylation, hydroxylation and subsequent glucuronidation. The major MT-45 metabolites identified in human in vitro studies and in authenticated human urine were phase I metabolites and should be incorporated as analytical targets to existing toxicological screening methods. Phase II glucuronidated metabolites were present in much lower proportions. Conclusions: 2F-MT-45 has been detected in a seized tablet for the first time. The metabolite identification data provide useful urinary metabolite targets for forensic and clinical testing for MT-45 and allows screening of urine for 2F-MT-45 and its major metabolites to determine its prevalence in case work.
AB - Purpose: The detection of a novel psychoactive substance, 2F-MT-45, a fluorinated analogue of the synthetic opioid MT-45, was reported in a single seized tablet. MT-45, 2F-, 3F- and 4F-MT-45 were synthesised and reference analytical data were reported. The in vitro and in vivo metabolisms of MT-45 and 2F-MT-45 were investigated. Method: The reference standards and seized sample were characterised using nuclear magnetic resonance spectroscopy, ultra-performance liquid chromatography–quadrupole time of flight mass spectrometry, gas chromatography–mass spectrometry, attenuated total reflectance-Fourier transform infrared spectroscopy and Raman spectroscopy. Presumptive tests were performed and physicochemical properties of the compounds determined. Metabolite identification studies using human liver microsomes, human hepatocytes, mouse hepatocytes and in vivo testing using mice were performed and identified MT-45 metabolites were confirmed in authentic human urine samples. Results: Metabolic pathways identified for MT-45 and 2F-MT-45 were N-dealkylation, hydroxylation and subsequent glucuronidation. The major MT-45 metabolites identified in human in vitro studies and in authenticated human urine were phase I metabolites and should be incorporated as analytical targets to existing toxicological screening methods. Phase II glucuronidated metabolites were present in much lower proportions. Conclusions: 2F-MT-45 has been detected in a seized tablet for the first time. The metabolite identification data provide useful urinary metabolite targets for forensic and clinical testing for MT-45 and allows screening of urine for 2F-MT-45 and its major metabolites to determine its prevalence in case work.
KW - Novel psychoactive substances
KW - MT-45
KW - 2F-MT-45
KW - Metabolite profiles
KW - Forensic Toxicology
KW - Clinical Toxicology
KW - Synthetic Opioids
KW - analytical chemistry
UR - http://www.scopus.com/inward/record.url?scp=85045059153&partnerID=8YFLogxK
U2 - 10.1007/s11419-018-0413-1
DO - 10.1007/s11419-018-0413-1
M3 - Article
C2 - 29963206
VL - 36
SP - 359
EP - 374
JO - Forensic Toxicology
JF - Forensic Toxicology
SN - 1860-8965
IS - 2
ER -