Abdallah Dahmani

In vitro characterization of potential CYP- and UGT-derived metabolites of the psychoactive drug 25B-NBOMe using LC-high resolution MS.

One of the main challenges posed by the emergence of new psychoactive substances is their identification in human biological samples. Trying to detect the parent drug could lead to false-negative results when the delay between consumption and sampling has been too long. The identification of their metabolites could then improve their detection window in biological matrices. Oxidative metabolism by cytochromes P450 and glucuronidation are two major detoxification pathways in humans. In order to characterize possible CYP- and UGT-dependent metabolites of the 2-(4-bromo-2,5-dimethoxy-phenyl)-N-[(2-methoxyphenyl)methyl]ethanamine (25B-NBOMe), a synthetic psychoactive drug, analyses of human liver microsome (HLM) incubates were performed using an ultra-high performance liquid chromatography system coupled with a quadrupole-time of flight mass spectrometry detector (UHPLC-Q-TOF/MS). On-line analyses were performed using a Waters OASIS HLB column (30 x 2.1 mm, 20 µm) for the automatic sample loading and a Waters ACQUITY HSS C18 column (150 x 2 mm, 1.8 µm) for the chromatographic separation. Twenty-one metabolites, consisting of 12 CYP-derived and 9 UGT-derived metabolites, were identified. O-Desmethyl metabolites were the most abundant compounds after the phase I process, which appears to be in accordance with data from previously published NBOMe-intoxication case reports. Although other important metabolic transformations, such as sulfation, acetylation, methylation or glutathione conjugation, were not studied and artefactual metabolites might have been produced during the HLM incubation process, the record of all the metabolite MS spectra in our library should enable us to characterize relevant metabolites of 25B-NBOMe and allow us to detect 25B-MBOMe users.

Vapour pressures and excess functions of N, N, N′, N′-tetramethylalkanediamine + cyclohexane. A group contribution study of the NN proximity effect

Abstract The vapour pressuresof liquid cyclohexane + N, N, N′, N′-tetramethylalkanediamine, (CH3)2 N(CH2)uN(CH3)2 (u = 1,2) + cyclohexane mixtures were measured by a static method between 303.15 and 343.15 K at 10 K intervals. The excess molar enthalpies at 303.15 K were also measured. The molar excess Gibbs energies, calculated from the vapour-liquid equilibrium data, and the molar excess enthalpies compare satisfactorily with group contribution (DISQUAC) predictions. The proximity effect of N atoms produces a regular decrease of the interactional parameters.

Excess properties of N,N,N′,N′-tetramethylalkanediamine + n-heptane: A study of the N-N proximity effect

Abstract The vapour pressure of liquid n -heptane + N , N , N ′, N ′ - tetramethylalkanediamine, (CH 3 ) 2 N-(CH 2 ) u _ N(CH 3 ) 2 ( u = 1,2), mixtures were measured by a static method in the 303.15–343.15 K range at 10 K intervals. The excess molar enthalpies were also measured at 303.15 K. The molar excess Gibbs energies, calculated from the vapour-liquid equilibrium data and the molar excess enthalpies compare satisfactorily with group contribution (DISQUAC) predictions. The proximity effect of N-atoms produces a regular decrease of the interaction parameters.

Vapour pressures and excess functions of 1,4-dimethylpiperazine + n-heptane, or cyclohexane measurement and prediction

Abstract The vapour pressures of liquid 1,4-dimethylpiperazine + n-heptane or cyclohexane mixtures were measured by a static method between 273.15 and 363.15 K at 10 K intervals. The excess molar enthalpies, at 303.15 K were also measured. The molar excess Gibbs energies, calculated from the vapour liquid equilibrium data, and the molar excess enthalpies compared satisfactorily with group contribution (DISQUAC) predictions. The quasi-chemical contribution to the N/alkane and N/c-CH2 contact improves the agreement. The intramolecular effects (ring effect, proximity effect) would then affect the quasi-chemical parameters, keeping the dispersives ones constant.

Measurement and prediction of solid–liquid phase equilibria for diamine + n-heptane, or cyclohexane

Abstract Solid–liquid equilibria (SLE) of N,N,N′,N′-tetramethylethylenediamine, 1,4-dimethylpiperazine and N,N-dimethylaniline+n-heptane or cyclohexane mixtures were measured by a static method. It was found that all systems are simple eutectic systems. Group contribution models have proved fairly successful in predicting SLE, however, the presence of intramolecular effects (ring effect, proximity effect) renders the widely used empirical methods quite inaccurate. However, in this work, the experimental phase diagrams compared satisfactorily with group contribution models (DISQUAC) and also modified UNIFAC (Dortmund version) predictions.