43 research outputs found
Chemical synthesis, characterisation and in vitro and in vivo metabolism of the synthetic opioid MT-45 and its newly identified fluorinated analogue 2F-MT-45 with metabolite confirmation in urine samples from known drug users
© 2018 The Author(s) 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
Determination of perhexiline and hydroxyperhexiline in plasma by liquid chromatography-mass spectrometry
A method for the quantitative determination of perhexiline and its main hydroxylated metabolites in human plasma, based on liquid chromatography-mass spectrometry (LC-MS), was developed. The method used protein precipitation with acetonitrile followed by dilution with water and subsequent direct injection of the extract into the LC-MS system. Hexadiline was used as internal standard and the intra-assay coefficients of variation were <or=5% for perhexiline and cis-hydroxyperhexiline over the target concentration range in patients. The lower limits of quantification were 0.005mg/l for perhexiline and 0.015mg/l for cis-hydroxyperhexiline, and the measuring ranges were from 0.05 to 3.0 and from 0.2 to 6.0mg/l, respectively. The method was compared with an established HPLC method with fluorescence detection and the correlation between the methods was close to 1 for both compounds. The predominant form of hydroxyperhexiline in 87% of the patient samples was found to be one of the diastereomeric pairs of cis-hydroxyperhexiline. In patients not forming this metabolite, trans-hydroxyperhexiline could be detected. We conclude that the present LC-MS method is suitable for use in a clinical routine laboratory