A High-Resolution Magic Angle Spinning NMR Study of the Enantiodiscrimination of 3,4-Methylenedioxymethamphetamine (MDMA) by an Immobilized Polysaccharide-Based Chiral Phase.

This paper reports the investigation of the chiral interaction between 3,4-methylenedioxy-methamphetamine (MDMA) enantiomers and an immobilized polysaccharide-based chiral phase. For that, suspended-state high-resolution magic angle spinning nuclear magnetic resonance spectroscopy (1H HR-MAS NMR) was used. 1H HR-MAS longitudinal relaxation time and Saturation Transfer Difference (STD NMR) titration experiments were carried out yielding information at the molecular level of the transient diastereoisomeric complexes of MDMA enantiomers and the chiral stationary phase. The interaction of the enantiomers takes place through the aromatic moiety of MDMA and the aromatic group of the chiral selector by π-π stacking for both enantiomers; however, a stronger interaction was observed for the (R)-enantiomer, which is the second one to elute at the chromatographic conditions.

The development of a specific and sensitive LC-MS-based method for the detection and quantification of hydroperoxy- and hydroxydocosahexaenoic acids as a tool for lipidomic analysis.

Docosahexaenoic acid (DHA) is an n-3 polyunsaturated fatty acid that is highly enriched in the brain, and the oxidation products of DHA are present or increased during neurodegenerative disease progression. The characterization of the oxidation products of DHA is critical to understanding the roles that these products play in the development of such diseases. In this study, we developed a sensitive and specific analytical tool for the detection and quantification of twelve major DHA hydroperoxide (HpDoHE) and hydroxide (HDoHE) isomers (isomers at positions 4, 5, 7, 8, 10, 11, 13, 14, 16, 17, 19 and 20) in biological systems. In this study, HpDoHE were synthesized by photooxidation, and the corresponding hydroxides were obtained by reduction with NaBH4. The isolated isomers were characterized by LC-MS/MS, and unique and specific fragment ions were chosen to construct a selected reaction monitoring (SRM) method for the targeted quantitative analysis of each HpDoHE and HDoHE isomer. The detection limits for the LC-MS/MS-SRM assay were 1-670 pg for HpDoHE and 0.5-8.5 pg for HDoHE injected onto a column. Using this method, it was possible to detect the basal levels of HDoHE isomers in both rat plasma and brain samples. Therefore, the developed LC-MS/MS-SRM can be used as an important tool to identify and quantify the hydro(pero)xy derivatives of DHA in biological system and may be helpful for the oxidative lipidomic studies.

Chiral separation of 3,4-methylenedioxymethamphetamine (MDMA) enantiomers using batch chromatography with peak shaving recycling and its effects on oxidative stress status in rat liver.

This work reports the multimiligram separation of 3,4-methylenedioxy-methamphetamine (MDMA) enantiomers using batch chromatography with peak shaving recycling. The effect of both enantiomers compared to the racemic mixture was examined on the oxidative stress status of rat liver. The enantiomeric purification was performed using a based cyclodextrin chiral selector and methanol:ammonium acetate buffer (pH 6.0, 100mM) (30:70, v/v) as mobile phase. The average mass rate obtained was 40.0mg/day, providing 45.0mg of the (R)-(-)-MDMA (e.r. 99.0%) and 75.0mg (e.r. 96.0%) of (S)-(+)-MDMA. Racemic MDMA and both enantiomers were administered per orally to Wistar rats and oxidative stress status parameters, as liver total glutathione levels and malondialdehyde (MDA) production in liver were evaluated. There was a significant decrease in hepatic glutathione content in the racemic MDMA and the (R)-(-)-MDMA-treated rats when compared to the control and to (S)-(+)-MDMA. These results demonstrate that the R-enantiomer is the enantiomer that contributes to the depletion of hepatic glutathione induced by the racemic mixture. The high reactivity of the R-enantiomer of MDMA in the liver can also be observed in animals treated with (R)-(-)-MDMA. The production of malondialdehyde (MDA) by (R)-(-)-MDMA was significantly higher when compared to the other treated groups and control.

Albendazole sulfoxide enantiomers: preparative chiral separation and absolute stereochemistry.

The enantiomeric separation of albendazole sulfoxide was carried out by simulated moving bed chromatography with variable zones (VARICOL). An overall recovery of 97% was achieved and enantiomeric ratios of 99.5% for raffinate and 99.0% for extract were attained. A total of 880 mg of (+)-albendazol sulfoxide and 930 mg of its antipode were collected after 55 cycles or 11 h of process, resulting in a mass rate of 2 g/day. Furthermore the absolute configuration of the enantiopure compounds was determined for the first time by vibrational circular dichroism (VCD) with the aid of theoretical calculations as (-)-(S) and (+)-(R)-albendazole sulfoxide.