Commercially available cathinones are drugs of long-term abuse drugs whose pharmacology is fairly well understood. While their psychedelic effects are associated with 5-HT2AR, the enclosed study ...summarizes efforts to shed light on the pharmacodynamic profiles, not yet known at the receptor level, using molecular docking and three-dimensional quantitative structure–activity relationship (3-D QSAR) studies. The bioactive conformations of cathinones were modeled by AutoDock Vina and were used to build structure-based (SB) 3-D QSAR models using the Open3DQSAR engine. Graphical inspection of the results led to the depiction of a 3-D structure analysis-activity relationship (SAR) scheme that could be used as a guideline for molecular determinants by which any untested cathinone molecule can be predicted as a potential 5-HT2AR binder prior to experimental evaluation. The obtained models, which showed a good agreement with the chemical properties of co-crystallized 5-HT2AR ligands, proved to be valuable for future virtual screening campaigns to recognize unused cathinones and similar compounds, such as 5-HT2AR ligands, minimizing both time and financial resources for the characterization of their psychedelic effects.
Headspace sampling is a fast, simple and economical way to prepare plant
samples for analysis by gas chromatography. For the first time, the
composition of the head space volatiles (HSV) of six ...Salvia species (S.
verticillata, S. glutinosa, S. nemorosa, S. aethiopis, S. amplexicaulis and
S. officinalis) in the flowering stage and two (S. glutinosa and S. sclarea)
in the fruiting stage from Southeastern Serbia was analysed using the
GC-FID-MS technique after headspace sampling. The chemical composition of
the highly volatile compounds of the analysed species varies considerably.
Monoterpene hydrocarbons represented the dominant class of volatile
compounds in all the Salvia species, except for S. sclarea and S. aethiopis.
The content of sesquiterpenes was the highest in S. aethiopis (96.9%) and S.
glutinosa in the flowering phase (29.5%), while in all the other samples
that percentage was below 10%. Oxygenated monoterpenes were the most
abundant in S. sclarea, where the main component was oxygenated monoterpene
linalyl acetate (97.7%). The main component of S. verticillata was
?-phellandrene, and its content varied depending on the plant location and
sampling time. The main component of S. glutinosa in the flowering phase was
limonene (16.6%), and in the fruiting phase sabinene (87.1%). Headspace
analysis of the volatile components of S. aethiopis was carried out for the
first time and the most abundant detected components were sesquiterpenes:
(E)- caryophyllene (36.8%), ?-copaene (33.4%) and ?-elemene (7.3%). The
analysis of the principal components was performed to interpret the grouping
patterns, as well as to analyse the similarities and differences between the
samples in terms of the composition of the volatile components. The samples
were grouped into three clusters. The first cluster consisted of samples of
S. verticillata (S1, S4 and S5) from different locations, the second
comprised samples of S. glutinosa (S3), S. aethiopis (S8), S. amplexicaulis
(S9) and S. officinalis (S10), while samples of S. nemorosa (S7) made up the
third cluster. The HS-GC-FID-MS technique can be successfully used for the
qualitative and quantitative analysis of volatile compounds of different
Salvia species. The obtained results are important for evaluating the
possibility of using different types of sage.
Alpha-amanitin is a cyclic peptide which belongs to a large group of mushroom toxins known as amatoxins. Being responsible for the majority of fatal mushroom poisonings, they require rapid detection ...and excretion from the body fluids. In accordance with these requirements, a simple and an accurate method was developed for successful identification and quantification of alpha-amanitin in serum with electrospray liquid chromatography–mass spectrometry (LC-ESI-MS) after collision-induced dissociation. The method conforms to the established International Conference on Harmonization Q2A/Q2B 1996 guidelines on the validation of analytical methods. Linearity, precision, extraction recovery and stability test on blank serum spiked with alpha-amanitin and stored in different conditions met the acceptance criteria. The obtained calibration curve was linear over the concentration range 5-100 ng/mL with a lower limit of quantification (LOQ) of 5 ng/mL and limit of detection (LOD) of 2.5 ng/mL. The mean intra- and inter-day precision and accuracy were 6.05% and less than ±15% of nominal values, respectively. The neutral solid phase extraction with copolymer hydrophilic–lipophilic balance cartridges was found optimal for sample preparation with the mean recovery of 91.94%. The proposed method demonstrated high sensitivity and selectivity which can be useful both for clinical and forensic toxicology analysis of alpha-amanitin at low concentrations.
A simple, cost-effective and fast headspace gas chromatography method coupled with flame ionization detection (HS-GC/FID) for determination of ethanol was developed and validated for clinical and ...forensic toxicology purposes. HS-GC/FID is often used for alcohol determination in different biological and non-biological samples. The calibration dependence of the method was linear in the range from 0.15 to 4.00 g dm-3 (r2=0.999) with adequate accuracy (99?106 %) and precision. The limit of detection (LOD) was 0.006 g dm-3. The method was quantitative (LOQ) above 0.020 g dm-3. The new method was successfully used for determination of ethanol in biological samples of intoxicated patients, car accidents participants, participants in criminal acts, and postmortem samples, non-biological samples such as alcoholic beverages, alcohol-based herbal preparations, cosmetic preparations, etc. This method is easy to perform, making it suitable not only for the routine applications in clinical biochemistry and forensic laboratories, but also in different fields of industry (e.g. for pharmaceutical preparations, cosmetics, dietary supplements, etc.). Some of the applications for ethanol determination in different samples related to various clinical-forensic cases are presented.
In this paper a simplified dissolution test was performed for the release of
ambroxol from tablets according to the European Pharmacopoeia. In vitro,
three different dissolution media; 0.1 M HCl pH ...1.2, acetate buffer (ABS) pH
4.5 and phosphate buffer (PBS) pH 6.8 were used for the simulation of the
gastrointestinal conditions at temperature of 37.0?0.5?C. The drug release
was evaluated by a new ultra - high performance liquid chromatography (UHPLC)
- tandem mass spectrometry (MS/MS) method. The method was validated to meet
requirements as per ICH guidelines which include linearity, specificity,
precision, accuracy and robustness. The corresponding dissolution profiles
showed more than 80% drug release within 30 minutes without significant
differences. Further, the developed and validated UHPLC-MS/MS method could
find a useful application in the process of production, quality control and
bioavailability/bioequivalence studies of new pharmaceutical formulations of
drugs in order to achieve a safe therapeutic efficacy.
Initially made for medical treatment for Parkinsonism, obesity, and depression, cathinones have become illegal drugs for the “recreational use”. The mechanism of action of synthetic cathinones ...consists of the inhibition of monoamine transporters. DFT (Density Functional Theory) calculations on the selected cathinones (3-FMC, 4-FMC, 4-MMC, Buphedrone, Butylone, Ethylone, MDPV, Methcathinone, and Methylone) were performed using B3LYP level of the Gaussian 09 program suite. The unscaled B3LYP/6–31G vibrational wavenumbers are in general larger than the experimental values, so the use of selective scaling was necessary. The calculated spectra of selected cathinones are in good correlation with the experimental spectra which demonstrates that DFT is a good tool for the prediction of spectra of newly synthesized and insufficiently experimentally characterised cathinones. Also, HOMO-LUMO (Highest Occupied Molecular Orbital-Lowest Unoccupied Molecular Orbital) analysis shows that 3-FMC possesses the minimum energy gap of 3.386 eV, and the molecule 4-FMC possesses the maximum energy gap of 4.205 eV among the investigated cathinones. It indicates that 3-FMC would be highly reactive among all the cathinones under investigation.
Ambroxol hydrochloride is an expectorant agent, successfully applied in
mucolytic therapy for acute and chronic bronchopulmonary diseases. The drug
regulates not only mucus secretion but also showed ...antioxidant,
anti-inflammatory and local anesthetic properties. To supplement the
pharmacokinetic and toxicological studies of ambroxol, a rapid ultra-high
performance liquid chromatography-tandem mass spectrometry method for the
quantitation of ambroxol in rabbit serum was developed. A validation of the
method was performed as per the ICH guidelines for the validation of
bioanalytical methods. The chromatographic separation was achieved in a
submicron Kinetex RP - C18 - column (2.1 mm x 50 mm, 1.3?m) using the no
buffer mobile phase. The ESI mass spectrometry in the MRM mode was used with
a typical transitions m/z 378.9?263.8 for ambroxol and m/z 455.2?165.0 for
IS. Linearity was determined with an average coefficient of determination
>0.999 over the dynamic range from 0.5 - 200 ng/mL with LOD and LOQ of 0.25
ng/mL and 0.5 ng/mL, respectively. The results of the intra- and inter-day
precision and accuracy determined in different days were all found to be
within the acceptable limits ?15%. The present method was successfully
applied to pharmacokinetic study in the rabbits after a single oral dose
administration.
Cortical theta burst stimulation (TBS) structured as intermittent (iTBS) and continuous (cTBS) could prevent the progression of the experimental autoimmune encephalomyelitis (EAE). The interplay of ...brain antioxidant defense systems against free radicals (FRs) overproduction induced by EAE, as well as during iTBS or cTBS, have not been entirely investigated. This study aimed to examine whether oxidative-nitrogen stress (ONS) is one of the underlying pathophysiological mechanisms of EAE, which may be changed in terms of health improvement by iTBS or cTBS. Dark Agouti strain female rats were tested for the effects of EAE and TBS. The rats were randomly divided into the control group, rats specifically immunized for EAE and nonspecifically immuno-stimulated with Complete Freund's adjuvant. TBS or sham TBS was applied to EAE rats from 14th-24th post-immunization day. Superoxide dismutase activity, levels of superoxide anion (O
), lipid peroxidation, glutathione (GSH), nicotinamide adenine dinucleotide phosphate (NADPH), and thioredoxin reductase (TrxR) activity were analyzed in rat spinal cords homogenates. The severity of EAE clinical coincided with the climax of ONS. The most critical result refers to TrxR, which immensely responded against the applied stressors of the central nervous system (CNS), including immunization and TBS. We found that the compensatory neuroprotective role of TrxR upregulation is a positive feedback mechanism that reduces the harmfulness of ONS. iTBS and cTBS both modulate the biochemical environment against ONS at a distance from the area of stimulation, alleviating symptoms of EAE. The results of our study increase the understanding of FRs' interplay and the role of Trx/TrxR in ONS-associated neuroinflammatory diseases, such as EAE. Also, our results might help the development of new ideas for designing more effective medical treatment, combining neuropsychological with noninvasive neurostimulation-neuromodulation techniques to patients living with MS.
Commercially available cathinones are drugs of long-term abuse drugs whose pharmacology is fairly well understood. While their psychedelic effects are associated with 5-HTsub.2AR, the enclosed study ...summarizes efforts to shed light on the pharmacodynamic profiles, not yet known at the receptor level, using molecular docking and three-dimensional quantitative structure–activity relationship (3-D QSAR) studies. The bioactive conformations of cathinones were modeled by AutoDock Vina and were used to build structure-based (SB) 3-D QSAR models using the Open3DQSAR engine. Graphical inspection of the results led to the depiction of a 3-D structure analysis-activity relationship (SAR) scheme that could be used as a guideline for molecular determinants by which any untested cathinone molecule can be predicted as a potential 5-HTsub.2AR binder prior to experimental evaluation. The obtained models, which showed a good agreement with the chemical properties of co-crystallized 5-HTsub.2AR ligands, proved to be valuable for future virtual screening campaigns to recognize unused cathinones and similar compounds, such as 5-HTsub.2AR ligands, minimizing both time and financial resources for the characterization of their psychedelic effects.
Background: The cannabis plant or marijuana has been used since ancient times for different purposes. An increase in the content of THC in cannabis has been observed worldwide, whereas the CBD ...content is dropping. This study’s main goal was to categorize marijuana suspected policies’ seizures (MSPS) based on the cannabinoid component concentrations concerning their potency and age. Methods: The samples were MSPS seized in southeast Serbia from April 2019 to April 2020. The cannabinoid content was determined using gas chromatography with mass spectrometry. Descriptive statistics were performed using Linux LibreOffice Calc. Results: All of the samples had a THC content higher than 0.3%, thus classifying the samples as marijuana according to the Serbian Law on Psychoactive Controlled Substances. The highest concentration of THC was 16.10%, while the lowest was 4.90%. The highest average concentration of THC (12.39%) was found in the buds. Only 11.81% of the samples had a CBD concentration higher than 1%, making all other marijuana samples extremely psychoactive. Most of the samples were older than 2 years, according to the calculated CBN/THC ratio. Conclusion: Our results confirm trends regarding the dominance of THC content in contemporary cannabis worldwide. It is necessary to monitor trends of cannabis potency in Serbia continuously because of its location.
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