Achiral LC-MS/MS and chiral SFC-MS methods for quantification of methoxphenidine and O-desmethyl-methoxphenidine metabolite in rat serum and brain.

Methoxphenidine (MXP), a dissociative anaesthetic derivative, has garnered the attention of toxicologists for their increasing abuse and associated toxicity. Despite that there is limited forensic and clinical toxicology data on MXP, especially regarding its metabolism and enantiomers. To fill this gap, we developed, validated and applied achiral liquid chromatography-tandem mass spectrometry (LC-MS/MS) and chiral supercritical fluid chromatography-MS (SFC-MS) methods to quantify MXP and its primary metabolite, O-desmethyl-methoxphenidine (dmMXP), in rat serum and brain samples collected after a single subcutaneous dosing of racemic MXP.

Liquid chromatography-inductively coupled plasma mass spectrometry analysis of peptides labelled with ClickZip mass tags.

Lipidated anorexigenic peptides are highly promising compounds for the treatment of obesity and related diseases. However, their exact mechanism of action still remains unknown. We labelled a lipidated analogue of an anorexigenic prolactin-releasing peptide (palm-PrRP31) with an extremely stable ClickZip lanthanide tag, facilitating tracking of the peptide within the organism.

Challenges of cannabidiol determination in emulsified cosmetics and application of solid-phase extraction followed by HPLC-UV-MS/MS.

The recent surge in popularity of cannabidiol-infused products extends beyond food and supplements to the cosmetic industry. Accurate labeling remains a significant concern, as many products fail to meet advertised cannabidiol content and/or contain psychoactive tetrahydrocannabinol above the permissible levels. In this work, we present the use of an HPLC-UV-MS/MS method for the quantification of five major cannabinoids (cannabidiol, cannabidiolic acid, tetrahydrocannabinol, tetrahydrocannabinolic acid, and cannabigerol) in oil-in-water cosmetic emulsions.

Simultaneous treatment with palm-LEAP2(1-14) and feeding high-fat diet attenuates liver lipid metabolism but not obesity: Sign of selective resistance to palm-LEAP2(1-14).

Liver-enriched antimicrobial peptide 2 (LEAP2) is a natural antagonist/inverse agonist of ghrelin receptor GHSR. Its truncated palmitoylated analog palm-LEAP2(1-14) promised anti-obesity properties because it exhibited favourable stability and an acute anorexigenic effect in our previous studies. Here we demonstrate desirable palm-LEAP2(1-14) pharmacokinetics, with significant levels of the peptide persisting in mouse blood 3 h after its subcutaneous administration.

Lipidized analogues of the anorexigenic CART (cocaine- and amphetamine-regulated transcript) neuropeptide show anorexigenic and neuroprotective potential in mouse model of monosodium-glutamate induced obesity.

Aims: This study investigates the neuroprotective effects of lipidized analogues of 2-SS-CART(61-102) derived from anorexigenic neuropeptide cocaine- and amphetamine-regulated transcript peptide (CARTp) in light of the link between obesity, its comorbidities, and the development of Alzheimer's disease.

Methods: We introduce novel lipidized analogues derived from 2-SS-CART(61-102), a specific analogue of natural CART(61-102), with two disulfide bridges. Using hypothermic PC12 cells, we tested the effect of the most potent analogues on Tau phosphorylation.

Ambient ionization mass spectrometry provides screening of selective androgen receptor modulators.

Ambient ionization mass spectrometry allows for analysis of samples in their natural state, i.e., with no sample pre-treatment.

Lipidization as a tool toward peptide therapeutics.

Peptides, as potential therapeutics continue to gain importance in the search for active substances for the treatment of numerous human diseases, some of which are, to this day, incurable. As potential therapeutic drugs, peptides have many favorable chemical and pharmacological properties, starting with their great diversity, through their high affinity for binding to all sort of natural receptors, and ending with the various pathways of their breakdown, which produces nothing but amino acids that are nontoxic to the body. Despite these and other advantages, however, they also have their pitfalls.

Combination of quinoxaline with pentamethinium system: Mitochondrial staining and targeting.

Pentamethinium indolium salts are promising fluorescence probes and anticancer agents with high mitochondrial selectivity. We synthesized two indolium pentamethinium salts: a cyclic form with quinoxaline directly incorporated in the pentamethinium chain (cPMS) and an open form with quinoxaline substitution in the γ-position (oPMS). To better understand their properties, we studied their interaction with mitochondrial phospholipids (cardiolipin and phosphatidylcholine) by spectroscopic methods (UV-Vis, fluorescence, and NMR spectroscopy).

Search for lipidized PrRP analogs with strong anorexigenic effect: In vitro and in vivo studies.

Prolactin-releasing peptide (PrRP) is an anorexigenic neuropeptide that attenuates food intake and increases energy expenditure. We designed three series of new lipidized PrRP31 analogs of different lengths of fatty acids attached at amino acids 1 or 11 directly or via linkers, part of them acetylated at the N-terminus and/or modified with dichlorophenylalanine (PheCl) at the C-terminus. We tested their affinity for and activation of signaling pathways relevant to receptors GPR10, NPFF-R2, and NPFF-R1, effect on food intake in fasted or freely fed mice and rats, and stability in rat plasma.

A Novel Truncated Liver Enriched Antimicrobial Peptide-2 Palmitoylated at its N-Terminal Antagonizes Effects of Ghrelin.

Ghrelin is secreted in the stomach during fasting and targets the growth hormone secretagogue receptor (GHSR1a) in the hypothalamus and brainstem to exert its orexigenic effect. Recently, liver enriched antimicrobial peptide-2 (LEAP2) was identified as an endogenous high-affinity GHSR1a antagonist. LEAP2 is a 40-amino acid peptide with two disulfide bridges and GHRS1a affinity in the N-terminal hydrophobic part.

Advanced microextraction techniques for the analysis of amphetamines in human breast milk and their comparison with conventional methods.

Breast milk analysis provides useful information about acute newborn exposure to harmful substances, such as psychoactive drugs abused by a nursing mother. Since breast milk represents a complex matrix with large amounts of interfering compounds, a comprehensive sample pre-treatment is necessary. This work focuses on determination of amphetamines and synthetic cathinones in human breast milk by microextraction techniques (liquid-phase microextraction and electromembrane extraction), and their comparison to more conventional treatment methods (protein precipitation, liquid-liquid extraction, and salting-out assisted liquid-liquid extraction).

MALDI Mass Spectrometry Imaging of Lipids on Free-Floating Brain Sections and Immunohistochemically Colocalized Markers of Neurodegeneration.

In mass spectrometry imaging (MSI), the essential steps in sample preparation include collection and storage. The most widely used preservation procedure for MSI consists in freezing samples and storing them at temperatures below -80 °C. On the other hand, the most common method for preserving biological samples in clinical practice is their fixation in paraformaldehyde.

Stability Study of Cannabidiol in the Form of Solid Powder and Sunflower Oil Solution.

Stability studies represent an essential component of pharmaceutical development, enabling critical evaluation of the therapeutic potential of an active pharmaceutical ingredient (API) or a final pharmaceutical product under the influence of various environmental factors. The aim of the present study was to investigate the chemical stability of cannabidiol (CBD) in the form of a solid powder (hereinafter referred to as CBD powder) and also dissolved in sunflower oil. We performed stress studies in accordance with the International Conference on Harmonization (ICH) guidelines, where 5 mg of marketed CBD in the form of a solid powder and in form of oil solution were exposed for 7 and 14, 30, 60, 90, 180, 270, and 365 days to precisely defined temperature and humidity conditions, 25 °C ± 2 °C/60% RH ± 5% and 40 °C ± 2 °C/75% RH ± 5% in both open and closed vials in the dark.

Iron Complexes of Flavonoids-Antioxidant Capacity and Beyond.

Flavonoids are common plant natural products able to suppress ROS-related damage and alleviate oxidative stress. One of key mechanisms, involved in this phenomenon is chelation of transition metal ions. From a physiological perspective, iron is the most significant transition metal, because of its abundance in living organisms and ubiquitous involvement in redox processes.

Comparison of Chemical Composition and Biological Activities of Eight Species.

P. Beauv. is a group of vascular plants in the family Selaginellaceae Willk.

New multimodal stationary phases prepared by Ugi multicomponent approach.

Eight different stationary phases based on two aminopropyl silicas of different brands suitable for multimodal chromatography applications have been prepared by a four-component Ugi reaction. The intention was to synthesize stationary phases significantly differing in their properties hereby demonstrating flexibility of the Ugi synthetic protocol. Diverse functional groups including a nonpolar long aliphatic chain, phenyl moiety, cholic acid scaffold, phenylboronic and monosaccharide units, charged betaine, and arginine moieties were immobilized on a silica surface.

Combination of UV and MS/MS detection for the LC analysis of cannabidiol-rich products.

Cannabidiol (CBD), a major non-psychoactive cannabinoid, has received a lot of attention due to its potential anti-inflammatory, pain-relieving, and anti-anxiety properties. This has led to a recent boom in CBD-rich commercial products, which are sold without prescription in the form of oils, candies, and cosmetics. Since these products are derived from cannabis, the presence of the psychoactive tetrahydrocannabinol (THC) has to be tested before they enter the market.

Mass spectrometry imaging of free-floating brain sections detects pathological lipid distribution in a mouse model of Alzheimer's-like pathology.

Mass spectrometry imaging (MSI) is a modern analytical technique capable of monitoring the spatial distribution of compounds within target tissues. Collection and storage are important steps in sample preparation. The recommended and most widely used preservation procedure for MSI is freezing samples in isopentane and storing them at temperatures below -80 °C.

Formaldehyde Reacts with Amino Acids and Peptides with a Potential Role in Acute Methanol Intoxication.

Methanol, an aliphatic alcohol widely used in the industry, causes acute and chronic intoxications associated with severe long-term health damage, including permanent visual impairment, brain damage, mainly necrosis of the basal ganglia and high mortality due to cancer. However, the role of formaldehyde, an intermediate metabolite of methanol oxidation, in methanol toxicity remains unclear. Thus, we studied the reactivity of several amino acids and peptides in the presence of formaldehyde by identifying products by direct infusion electrospray high-resolution mass spectrometry (MS) and matrix-assisted laser desorption-ionization MS.

Synthesis and identification of deschloroketamine metabolites in rats' urine and a quantification method for deschloroketamine and metabolites in rats' serum and brain tissue using liquid chromatography tandem mass spectrometry.

Deschloroketamine (2-(methylamino)-2-phenyl-cyclohexanone) is a ketamine analog belonging to a group of dissociative anesthetics, which have been distributed within the illicit market since 2015. However, it was also being sold as 'ketamine' misleading people to believe that they were getting genuine ketamine. Dissociative anesthetics have also come to the attention of the psychiatric field due to their potential properties in the treatment of depression.