The study of the biotransformation of a new synthetic drug 2,5-dimethoxy-4-bromamphetamine (DOB) and identification of its metabolites in urine of a poisoned person is described using gas chromatography mass spectrometry (GC-MS) with various ways of derivatization. It has been confirmed that one of its metabolic pathways leads to the corresponding 2-O-desmethyl and 5-O-desmethyl metabolites when the latter is prevailing. It is important to know the metabolism of this neurotoxic and hallucinogenic substance as it is a prerequisite for developing reliable toxicological diagnostic procedures and for assessment of toxicological risks.
Deoxynivalenol (DON) is one of the most common mycotoxins produced by field fungi (especially Fusarium). Contamination of livestock feed is a significant risk factor, especially for pigs that are highly susceptible to the toxic effects of deoxynivalenol. In this study, validated ultra-high performance liquid chromatography (U-HPLC) combined with a HR-Orbitrap-MS analysis method is described for the identification and quantitative determination of the mycotoxin compounds (DON and deepoxy-deoxynivalenol (DOM-1)) in pig colostrum (milk) and serum. Pre-treatment of the samples involved a deproteinisation step with methanol followed by a purification step by solid phase extraction (HLB cartridges). The chromatographic separation was performed on a C18 column with 1.7 μm-particle size using a water-methanol mobile phase. Detection of analytes was achieved on the tandem hybrid mass spectrometer Q Exactive, with a heated electrospray ionisation probe measured in positive mode (H-ESI+). For the confirmation of identification, a mass spectrometer was utilized in the full scan mode with resolving power (PR) = 140,000 (FWHM) and for quantification analysis, it was utilized in the parallel reaction monitoring mode (PRM). The method has been fully validated according to the requirements of Commission Decision 2002/657/EC for confirmatory analyses, plus the addition of a mass accuracy (MA) parameter. For the confirmation of the presence of these analytes in pig colostrum and serum, matching of the retention time with mass accuracy for the precursor ion from MS and product ions from MS/MS was used. A deuterium isotopically labelled internal standard and a matrix-matched calibration curve were employed for quantification. The linear range of quantification was 0.5-20 μg L-1 and the correlation coefficient (R2) was >0.999 for all calibrations. The limit of detection for DON and DOM-1 in colostrum was 0.48 μg L-1 and 0.54 μg L-1, respectively, and in serum 0.24 μg L-1 and 0.36 μg L-1, respectively. The limit of quantification for DON and DOM-1 in colostrum was 0.80 μg L-1 and 0.89 μg L-1, respectively, and in serum 0.39 μg L-1 and 0.60 μg L-1, respectively. The method was successfully evaluated using the obtained samples of pig colostrum and serum.
- MeSH
- chromatografie kapalinová metody MeSH
- kolostrum chemie MeSH
- kontaminace potravin analýza MeSH
- krmivo pro zvířata MeSH
- limita detekce MeSH
- lineární modely MeSH
- prasata MeSH
- reprodukovatelnost výsledků MeSH
- tandemová hmotnostní spektrometrie metody MeSH
- těhotenství MeSH
- trichotheceny analýza MeSH
- zvířata MeSH
- Check Tag
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
2,5-Dimethoxy-4-bromoamphetamine (DOB) is one of the potent hallucinogenic phenylalkylamines, whose ingestion has already caused several deaths reported all over the world. However, there is insufficient information on DOB properties based on controlled pharmacokinetic studies available. The aim of this study was to clarify the distribution profile of DOB and its phenolic metabolite 2-methoxy-5-hydroxy-4-bromoamphetamine (2M5H4BA) in blood and biological tissues of experimental rats. The rats were administered a 20 mg/kg dose of DOB.HCl by oral ingestion or subcutaneous injection. Plasma and brain, liver and lung tissues were collected at 0.5, 1, 2, 4, 8, 16, and 32 h after dosing (three animals per time point). The samples were prepared by a liquid-liquid extraction procedure and the extracts were assayed by GC-MS. After per oral application, DOB peak plasma level of 320 ng/mL was reached after one-hour post dosing as well as 2M5H4BA peak concentration of 203 ng/mL. A rapid phase of DOB absorption, 2M5H4BA formation and their tissue distribution during the first two hours after application were followed by a slow decrease rate of the elimination process until 32 h. After subcutaneous application, high plasma levels of the unchanged parent drug and relatively reduced formation of its metabolite 2M5H4BA were observed. DOB maximum plasma concentration of 1143 ng/mL was reached after one-hour post application, whereas its metabolite peak level after 8 h was 213 ng/mL. The concentration profiles of both compounds in plasma after per oral and subcutaneous administration revealed the existence of significant first pass effect after per oral administration that significantly affected DOB bioavailability. DOB tissue concentrations exceeded plasma and the highest values were found in the lungs, where drug accumulation occurred with prolonged retention till 32 h after subcutaneous dose. Although the plasma/tissue transfer was more effective for the lipophilic parent drug than for its hydroxylated metabolite 2M5H4BA, the metabolite tissue levels were significant. The hallucinogenic potential of 2M5H4BA appearing in brain remains unclear as nothing is known about its pharmacological activity at present.
- MeSH
- 2,5-dimethoxy-4-methylamfetamin aplikace a dávkování analogy a deriváty farmakokinetika krev MeSH
- aplikace orální MeSH
- financování organizované MeSH
- halucinogeny aplikace a dávkování farmakokinetika krev MeSH
- injekce subkutánní MeSH
- játra chemie MeSH
- krysa rodu rattus MeSH
- mozek - chemie MeSH
- plíce chemie MeSH
- plynová chromatografie s hmotnostně spektrometrickou detekcí MeSH
- potkani Wistar MeSH
- soudní toxikologie MeSH
- tkáňová distribuce MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
The psychedelic compound 4-bromo-2,5-dimethoxyphenethylamine (2C-B) has appeared as an agent in drug abuse or overdose cases in humans. The human pharmacokinetics of this drug is unknown and only partial information is available on its metabolites. Our experimental study was focused on the disposition and kinetic profile of 2C-B in rats after subcutaneous administration using a GC-MS validated method. One of the major metabolites 4-bromo-2-hydroxy-5-methoxyphenethylamine (2H5M-BPEA) was confirmed in rat tissues of lung, brain, liver and was quantitatively evaluated as well. The disposition of 2C-B was characterized by its estimated half-life 1.1h and estimated volume of distribution 16L/kg. The lung susceptibility for drug retention and gradual temporal release parallel to the brain were ascertained. The drug penetrating the blood/brain barrier was without significant delay. 2C-B brain to serum ratio attained a maximum value of 13.9 and remained over the value of 6.5 to the end of our observation (6h after the dose). The distribution of the hydroxylated metabolite 2H5M-BPEA into the lipophilic brain tissue was less efficient in relation to the parent compound. The kinetics of the drug partitioning between blood to brain may be important for the subsequent assessment of its psychotropic or toxic effects.
- MeSH
- 2,5-dimethoxy-4-methylamfetamin analogy a deriváty farmakokinetika krev MeSH
- aplikace kožní MeSH
- dimethoxyfenylethylamin analogy a deriváty farmakokinetika krev MeSH
- financování organizované MeSH
- játra metabolismus MeSH
- krysa rodu rattus MeSH
- mozek metabolismus MeSH
- plíce metabolismus MeSH
- potkani Wistar MeSH
- psychotropní léky farmakokinetika krev MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
Nová porodnice v Nové Bani zřízena dle sovětského vzoru v r. 1952. Celkový vzestup zdravotnické péče ve městě. Zmínka o malých venkovských porodnicích a jejich poslání
