A method of analysis was developed for the simultaneous chemo- and enantioseparation of 2-, 3-, and 4-chloromethcathinones by high-performance liquid chromatography tandem mass-spectrometry. The fast ...method enables the reliable identification of positional isomers of chloromethcathinones in biological samples. In addition, the same method can be used for the enantioselective quantitative determination of one of these compounds and its major phase-1 metabolites in biological fluids. The developed method was applied to oral fluid samples collected by police during routine random traffic control in Belgium from January to November, 2023. It was found that 3-CMC was more frequently abused compared to 4-CMC. Although some differences were observed between the concentrations of enantiomers in OF, most likely the drugs were abused in the racemic form. No abuse of 2-CMC was detected at the timepoint of sample collection.
•Simultaneous separation of CMC positional isomers and their enantiomers.•Method applied to human oral fluid samples.•Identification of major phase-1 metabolites of CMCs.
Five immobilized-type chiral columns were prepared from linear, cyclic, and hyperbranched amylose tris(n-octadecylcarbamate) (ATODC) and amylose tris(n-butylcarbamate) (ATBC). A small amount of the ...linker site, 3-(triethoxysilyl)propylcarbamate, significantly reduced the chain dimensions of ATBC for which high chain stiffness is attained by intramolecular hydrogen bonding between butylcarbamate groups located on the neighboring glycosidic residue. This phenomenon was not found for ATODC, which is mainly stiffened by bulky side groups. While both columns have appreciable chiral recognition ability, number of separated racemates decreased with decreasing side group bulkiness. The bulkiness of the side groups thus plays a definite role in the chiral separation ability. Furthermore, chain linearity on the silica surface is an important factor for the chiral separation because no substantial chiral separation was found for the chiral columns consisting of cyclic ATODC and cyclic ATBC. The chiral column made of hyperbranched ATODC has an intermediate chiral separation ability between linear and cyclic ATODC, supporting this suggestion.
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•Immobilized columns were prepared from linear and cyclic ATBC and ATODC.•Linker groups of ATBC loosen the rigid helical main chain in solution.•Chiral separation ability increases with increasing side-chain bulkiness.•Chain linearity is a key factor of the chiral separation ability.•Hyperbranched ATODC has intermediate chiral separation ability.
Series of chiral palladium(II) allyl and cinnamyl complexes bearing a C1‐symmetric N‐heterocyclic carbenes were synthesized from achiral precursors. The chirality of theses complexes results from the ...formation of the carbene‐palladium bond which restricts the rotation of dissymmetric N‐aryl substituents of the NHC and thus creates an axis of chirality. Chiral HPLC at preparative scale enabled the resolution of racemic complexes and provided a straightforward access to complexes with excellent enantiopurities (>99.5% ee). Enantiopure complexes were studied by crystal X‐ray diffraction and electronic circular dichroism (ECD). Their configuration stabilities were investigated both experimentally and theoretically through the determination of the rotational barrier values. These complexes were tested for the intramolecular α‐arylation of amides, with a moderate chiral induction (up to 54% ee).
•An enantioselective method for quantification of methylone and some of its metabolites in oral fluid.•The method is simple and fast.•The method was applied for the enantioselectivity in metabolism ...and pharmacokinetic.
In the present study an enantioselective high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the first time for quantitative determination of the recreational drug of abuse methylone and its major metabolites in oral fluid. The simultaneous chemo- and enantioseparation of methylone and its major metabolites was performed on a polysaccharide-based chiral column based on amylose tris(5-chloro-3-methylphenylcarbamate) as chiral selector (Lux i-Amylose-3) with methanol containing 0.4 % (v/v) aqueous ammonium hydroxide as mobile phase. The time required for enantioselective analysis of methylone and its 2 major metabolites was 15 min. This method was fully validated following the Organization of Scientific Area Committees (OSAC) for Forensic Science guidelines.
This method was applied for the enantioselective determination of methylone and its metabolites in oral fluid and enantioselectivity in metabolism and pharmacokinetic of the parent compound and metabolites was observed.
While the first enantiomer of methylone was found at higher concentration, both metabolites shown greater concentration for the second enantiomer. The results revealed that MET undergoes an enantioselective biotransformation to its metabolites HMMC and MDC, with S-(−)-MET more rapidly metabolized and eliminated from the body.
In the present study enantioselective high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods were developed for the quantitative determination of ...3,4-methylenedioxy-methamphetamine (MDMA) and its major phase-1 metabolites 4-hydroxy-3-methoxyamphetamine (HMA), 4-hydroxy-3-methoxymethamphetamine (HMMA) and 3,4-methylenedioxyamphetamine (MDA) in human plasma, sweat, oral fluid (OF) and urine. The simultaneous separation of all these compounds and their respective enantioseparation was accomplished on two polysaccharide-based chiral columns. The Lux AMP column with a proprietary chiral selector enabled baseline separation of the enantiomers of MDMA, HMA and HMMA while MDA enantiomers could not be separated with this column under the experimental conditions used in this study. The Lux i-Amylose-3 column based on amylose tris(5-chloro-3-methylphenylcarbamate) as chiral selector baseline-separated the enantiomers of MDMA, HMMA and MDA while the enantiomers of HMA could not be separated. Thus, the various samples were analyzed by using both columns alternatively in combinations with acetonitrile containing 25% (v/v) 5 mM ammonium bicarbonate buffer at pH 11.0 as mobile phase. Analysis time was less than 4 min with the Lux AMP column and less than 6 min with the Lux i-Amylose-3 column. Both methods were validated and applied to the enantioselective determination of MDMA and its phase-I metabolites in human biological fluids, and enantioselective metabolism of MDMA was confirmed.
•An enantioselective method for quantitative determination of MDMA and some of its metabolites in human biological fluids.•The method is simple and fast, allowing high-throughput analyses.•The method was applied for the enantioselectivity in metabolism and pharmacokinetic of the parent compound and metabolites.
Seven undescribed compounds, dentipellinones A‒D (1, 2, 5, and 6), dentipellinol (3), methoxyerinaceolactone B (4), and erinaceolactomer A (7), were isolated from the culture broth of Dentipellis ...fragilis. Chemical structures of these isolated compounds were determined by analyses of 1D and 2D-NMR and MS data in comparison with data reported in the literature. Absolute configurations of 1‒7 were also determined by Electronic Circular Dichroism calculations. The isolated compounds were evaluated for their anti-inflammatory effects on NO production and pro-inflammatory cytokines levels in LPS-stimulated RAW264.7 cells. Compounds 5 and 7 were evaluated for their anti-inflammatory effects on NO production and pro-inflammatory cytokine levels in LPS-stimulated RAW264.7 cells. They exhibited inhibitory effects on LPS-induced NO production in a dose-dependent manner, and significantly reduced the levels of inflammatory-related cytokines such as IL-1β and IL-6. TNF-α was not involved in the anti-inflammatory effects of these compounds. Finally, compounds 5 and 7 showed significant anti-inflammatory effects.
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•Seven undescribed isobenzofuranone derivatives were isolated from the culture broth of Dentipellis fragilis.•Their chemical structures were determined by NMR and calculated ECD.•Compounds 5 and 7 showed potent inhibition of NO production and pro-inflammatory cytokine levels.•The results provide insight into the chemodiversity of Dentipellis fragilis.
•Synthesis and immobilization methods of polysaccharide derivatives.•Efficient immobilization of polysaccharide derivatives bearing trialkoxysilyl groups.•Application of the immobilized chiral ...packing materials (CPMs).•Versatility of eluent selection overcomes the defect of immobilized CPMs.•Racemic compounds resolved on immobilized CPMs.
Polysaccharide-based chiral stationary phases (CSPs) or chiral packing materials (CPMs) have been frequently employed for analyzing and separating various enantiomers by high-performance liquid chromatography (HPLC). The polysaccharide derivatives dissolved in a solvent are usually coated on silica gel to be used as CSPs. This means that some solvents, which can swell or dissolve the derivatives, cannot be used as the eluents in HPLC. In this review, various immobilization methods of the polysaccharide derivatives are described. The immobilization often reduces the chiral recognition ability compared to that of the corresponding coated-type CSPs. This problem can be overcome by the versatility of eluent selection for the immobilized CSPs. Enantioseparations of various racemates on the immobilized commercial columns using the non-standard eluents are briefly summarized.
Direct enantiomer separation of denopamine (DP, active form: R (-)-form), which is an optically active and an orally administrable cardiotonic agent, was investigated by HPLC with β-cyclodextrin ...(β-CD) immobilized chiral stationary phases (CSPs). Successful enantiomer separation under the reversed-phase mode was achieved by a β-CD having a phenyl moiety immobilized CSP with large resolution within 10 min. Optical purity testing and assay of tablets by the HPLC method developed were validated for specificity, linearity, and recovery. Validation results indicate the method is accurate and has a good linearity and sensitivity. Limit of detection and limit of quantitation of the minor enantiomer were 0.01% and 0.03%, respectively. Assay of DP tablets 5 mg by the internal standard method was also successfully achieved within 10 min. Further, photostability of DP was evaluated by this chiral HPLC method and the reversed-phase HPLC with an ODS column. Chemical structures of two photoproducts generated in an aqueous media were determined by LC-MS/MS, showing these were p-hydroxybenzaldehyde and 3,4-dimethoxyphenethylamine. Other than these two main photoproducts, low level (0.17%) of the minor enantiomer was detected.
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