Competition of zinc(II) with cadmium(II) or mercury(II) in binding to a 12-mer peptide

Speciation of the complexes of zinc(II) with a dodecapeptide (Ac-SCPGDQGSDCSI-NH2), inspired by the metal binding domain of MerR metalloregulatory proteins, have been studied by pH-potentiometric titrations, UV, SRCD (synchrotron radiation circular dichroism) and 1H NMR experiments. (MerR is a family of transcriptional regulators the archetype of which is the Hg2+-responsive transcriptional repressor-activator MerR protein.) The aim of the ligand-design was to retain the advantageous metal binding features of MerR proteins in a model peptide for the efficient capture of toxic metal ions. The peptide binds zinc(II) via two deprotonated Cys-thiol groups and one of the Asp-carboxylates in the ZnL parent complex, possessing a remarkably high stability (logK = 9.93). In spite of the relatively long peptide loop, bis-complexes are also formed with the metal ion under basic conditions. In a competition with cadmium(II) or mercury(II), zinc(II) cannot prevent the binding of toxic metal ions by the thiolate donor groups of the ligand. Around neutral pH one equivalent of mercury(II) was shown to fully replace zinc(II) from the ZnL species. Partial replacement of zinc(II) from the peptide by one equivalent of cadmium(II), relative to zinc(II) and the ligand, is also presumable, nevertheless, spectroscopic data may suggest the formation of mixed metal ion complexes, as well. Based on the obtained results the investigated dodecapeptide can be a promising candidate for capturing toxic metal ions in practical applications

Transport study of kynurenic acid and its newest derivatives through and in vitro model of the blood-brain barrier using targeted UHPLC-MS\MS

We have developed a targeted UHPLC-ESI–MS/MS method for the quantification of kynurenic acid (KYNA) and its derivatives from biological samples. The samples were gained from in vitro permeability assay. We have found that the transportation of the derivatives through the blood-brain barrier is better than KYNA

Analysis of oxylipins in human plasma: Comparison ofultrahigh-performance liquid chromatography andultrahigh-performance supercritical fluid chromatography coupled tomass spectrometry

tThe potential of ultrahigh-performance liquid chromatography–mass spectrometry (UHPLC/MS) andultrahigh-performance supercritical fluid chromatography (UHPSFC) coupled to negative-ion electro-spray ionization mass spectrometry (ESI–MS) for the analysis of 46 oxylipins and 2 fatty acid standardsis compared in terms of their chromatographic resolution with the emphasis on distinguishing isobaricinterferences and the method sensitivity. UHPLC provides the baseline separation of 24 isobaric oxylipinswithin 13 min, while UHPSFC enables the separation of only 20 isobaric oxylipins within 8 min. More-over, the UHPLC/ESI–MS method provides an average improvement of sensitivity by 3.5-fold. A similartrend is observed in the analysis of human plasma samples, but lower ion suppression effects causedby lysophospholipids (LPL) are observed in case of UHPSFC/ESI–MS due to better separation of LPL. Bothmethods are fully applicable for the analysis of oxylipins, but UHPLC/ESI–MS method is preferred dueto better separation and higher sensitivity, which results in the identification of 31 oxylipins in humanplasma based on available standards and additional tentative 20 identifications based on accurate m/zvalues and the fragmentation behavior known from the literature

Identification of the main metabolites of three synthetic cannabinoids using LC-MS/MS technique

The consumption of designer drugs today is a serious problem, especially among young people involvement. ‘Herbal mixtures’ containing synthetic cannabinoids (SCs) that mimic the effect of marijuana and there are easily available via the Internet. For analysis of urine samples, knowledge of the main metabolites is necessary as the mother compounds are usually not found in urine after using, due to their fast metabolism. The aims of this study were the in vitro identification of metabolites of ADB-FUBINACA, 5F-MDMB-PICA and CUMYL-PEGACLONE and to determine which analytical targets are excreted into urine. Metabolites identified after incubation of SCs with pooled human liver microsomes (HLM). The authentic urine samples were analysed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) for investigation of the major in vivo metabolites. The main metabolites were the mono-hydroxylation of ADB-FUBINACA and CUMYL-PEGACLONE in positive urine specimens. We didn’t have positive sample of 5F-MDMB-PICA

Analysis of new synthetic cannabinoid in human urine by LC-MS/MS

Synthetic cannabinoids (SCs) are a group of novel psychoactive substances, which bind to cannabinoid receptors (CB1 and CB2). One of the largest groups of SCs are smoking mixtures, which are intended as legal replacements of cannabis and distributed on the illicit drug market. In 2016, 11 new SCs were reported by the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). The most commonly used techniques for quantitation of SCs in urine are high performance liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). In this study we analysed in 2016-2017 released 6 new SCs such as 5F-MN18, AMB-CHMINACA, AMB-FUBINACA, APP-CHMINACA, CUMYL-4CNBINACA and THJ-2201. The LC-MS/MS system was optimised and the mass of identified parent ions, daughter ions and related retention time were determined. Matrix effect, extraction recovery and process efficiency were evaluated by the method proposed by Matuszewski et al