The enantiomers of trans-paroxetine (the selectand) were separated on four chiral stationary phases incorporating either quinine [ZWIX(+), ZWIX(+A)] or quinidine [ZWIX(-), ZWIX(-A)] and (R,R)-aminocyclohexanesulfonic acid [in ZWIX(-), and ZWIX(+A)] or (S,S)-aminocyclohexanesulfonic acid [in ZWIX(+), and ZWIX(-A)] chiral selectors. The zwitterion nature of the phases is due to the presence of either (R,R)- or (S,S)-aminocyclohexanesulfonic acid in the selector structure bearing the quinuclidine moiety. ZWIX(+) and ZWIX(-) phases are available on the market with the commercial names CHIRALPAK ZWIX(+) and CHIRALPAK ZWIX(-), respectively. With the aim of rationalizing the enantiomer elution order with the above chiral stationary phases, a molecular dynamic protocol was applied and two energetic parameters were initially measured: selectand conformational energy and selectand interaction energy. In the search for other descriptors allowing a better fitting with the experimental evidences, in the present work we consider an energetic parameter, defined as the selector conformational energy, which resulted to be relevant in the explanation of the experimental elution order in most of the cases. Very importantly, the computational data produced by the present study strongly support the outstanding role of the conformational energy of the chiral selector as it interacts with the analytes.
Dvacetiletá žena byla nalezena mrtvá ve svém pokoji. Byla medikamentózně léčena pro depresivní a panické poruchy, a opakovaně se pokoušela o suicidium. V blízkosti těla bylo nalezeno mnoho balení předepsaných léčiv, včetně paroxetinu. Při pitvě byly plíce edematózní. Orgány vykazovaly známky mírné kongesce a změny způsobené rozkladem. Autolýzou způsobená ruptura, označená jako gastromalacie, byla popsána na přední části stěny žaludku v oblasti kardie. Toxikologické vyšetření stanovilo 0,78, 3,20 a 17,63 µg/ml paroxetinu v kardiální, respektive femorální krvi a v moči. Acetaminophen a phenobarbital byly také stanoveny, a to v terapeutické či subletální koncentraci. Autoři vyhodnotili údaje získané post mortem, při čemž vzali v úvahu posmrtnou difuzi léků a došli k závěru, že smrt byla způsobena toxicitou paroxetinu spolu se serotoninovým syndromem.
A female in her twenties was found dead in her room. She had received medications for depression and panic disorder, and had attempted suicide several times. Many packets of prescribed drugs, including paroxetine, were found near the corpse. At autopsy, the lungs were edematous. The organs were slightly congested with putrefactive change. Autolytic rupture, considered as gastromalasia, was observed in the anterior cardiac portion of stomach wall. Toxicological examination revealed 0.78, 3.20 and 17.63 µg/ml of paroxetine in the heart blood, femoral blood and urine, respectively. Acetaminophen and phenobarbital were also identified within therapeutic or sub-lethal levels. Taking into consideration postmortem diffusion of drugs, we evaluated postmortem data and concluded that the death was mainly due to toxicity of paroxetine with serotonin syndrome.
- MeSH
- benzodiazepiny izolace a purifikace toxicita MeSH
- lidé MeSH
- mladý dospělý MeSH
- nežádoucí účinky léčiv MeSH
- otrava diagnóza etiologie patologie MeSH
- paracetamol izolace a purifikace toxicita MeSH
- paroxetin izolace a purifikace toxicita MeSH
- pitva metody MeSH
- posmrtné změny MeSH
- selektivní inhibitory zpětného vychytávání serotoninu izolace a purifikace toxicita MeSH
- serotoninový syndrom diagnóza MeSH
- soudní patologie MeSH
- Check Tag
- lidé MeSH
- mladý dospělý MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
