A Fatal Case of Pentedrone and α-Pyrrolidinovalerophenone Poisoning.

We report a fatal case of combined α-pyrrolidinovalerophenone (α-PVP) and 2-(methylamino)-1-phenylpentan-1-one (pentedrone) poisoning. A 28-year-old man was taken to hospital in asystole. Despite resuscitation efforts over 30 min, he died. The forensic autopsy showed pulmonary edema and moderately advanced atherosclerotic lesions of the arteries. Microscopic observation revealed chronic changes in the heart. Confirmation of the presence of pentedrone, α-PVP, and its metabolite 1-phenyl-2-(pyrrolidin-1-yl)pentan-1-ol (OH-α-PVP) in tissues and fluids were achieved using gas chromatography-mass spectrometry analysis after liquid-liquid extraction. A quantitative validated liquid chromatography-mass spectrometry method was used to determine the concentrations of the above designer drugs in postmortem samples. Pentedrone, α-PVP, and OH-α-PVP concentrations were 8,794, 901 and 185 ng/mL in whole blood, respectively; 100,044, 2,610 and 2,264 ng/g in the liver, respectively; 22,102, 462 and 294 ng/g in the kidney, respectively; 13,248, 120 and 91 ng/g in the brain, respectively and 500,534, 4,190 and 47 ng/g in the stomach contents, respectively. This is the first known reported death attributed to the combined use of α-PVP and pentedrone. Additionally, this article is the first to report the distribution of pentedrone in postmortem human samples.

Search for association between suicide and 5-HTT, MAOA and DAT polymorphism in Polish males.

A better understanding of genetic determinants of suicidal behavior might be very useful in clinical practice. The objectives of the present study were to answer the question whether there is an association between functional polymorphic forms of 5-HTT, MAOA or DAT and suicidality, and to examine whether the combination of functional alleles in 5-HTT, MAOA and DAT genes would predict a predisposition to suicidal behavior. Functional polymorphisms in 5-HTT, MAOA and DAT genes were investigated in 66 male suicide completers and 51 male control subjects from the Polish population. There were no significant differences in the allele and genotype frequencies between the case and control group. In the individual genotype tests, examination of the distribution differences of each genotype showed that genotype (3;12-12;S-S;9-10) differed between the suicide victims and control subjects. This genotype existed only in the control sample and appeared with the frequency of 8% (p = 0.03).

[Development of a method for estimation of citalopram and desmethylcitalopram in nails and hair and its usefulness in forensic toxicology]. / Opracowanie metody oznaczania citalopramu i desmetylocitalopramu w paznokciach i wlosach i jej wykorzystanie w toksykologii sadowej.

The report presents the possibility of using an alternative material of determining citalopram and its metabolite (desmethylcitalopram) in hair and nails. Citalopram (Cipramil, Citaratio, Citaxin, Oropram, Cital, Cilon, Aurex) is an antidepressant drug of the selective serotonin reuptake inhibitor (SSRI) class, employed in treatment of depression, prevention of depressive disorders recurrence and in some anxiety disorders. The investigations were performed using liquid chromatography coupled with electrospray-ionization mass spectrophotometry (LC-ESI-MS). In the course of the study, the authors developed a method for isolation and identification of Citaprolam and its metabolite (desmethylcitaprolam) from hair and nails. Determination were performed in hair and nail samples collected from individuals who had been administered citalopram in therapeutic doses at least for 12 months before sample collection. Hair and nail samples were obtained 4, 6, 9 and 15 months after discontinuing drug administration. The concentration of citalopram in nails was 0.40-10.49 ng/mg and the concentration of desmethylcitalopram was 0.32-3.70 ng/mg. In hair, citalopram concentration was 1.04-8.69 ng/mg and for desmethylcitalopram, the concentration range was 0.07-1.27 ng/mg.

Morphine inhalation by cancer patients: a comparison of different nebulization techniques using pharmacokinetic, spirometric, and gasometric parameters.

Despite numerous case reports suggesting the value of morphine (M) nebulization in the treatment of breathlessness, only a few clinical trials have been able to support this. The reason for this could lie in the lack of understanding of the localization of opioid receptors in the airways and the biopharmaceutics and pharmacokinetics of nebulized morphine. In the present study, we compared two different methods of pneumodosimetric nebulization: the Bronchial Control Treatment System-Sidestream (BCTS-S) and the Bronchial Control Treatment System-Micro Cirrus (BCTS-MC). The first method delivers relatively large aerosol particles (2-5microm) preferentially to the bronchial tree and trachea. In the BCTS-MC method, small aerosol particles (0.5-2microm) mostly reach the alveoli. Ten patients with cancer were randomly assigned to either the BCTS-S or BCTS-MC inhalation of 5 mg morphine HCl. Patients using the BCTS-S method inhaled a morphine dose in 6.6+/-2 minutes, whereas with the BCTS-MC method, the inhalation time was 28.8+/-8 minutes. The areas under the curve of morphine and glucuronides were several times higher after BCTS-S than after BCTS-MC. The proportion of morphine-3-glucuronide to morphine-6-glucuronide (M6) was, on average, close to one for both methods. From the same amount of morphine in the BCTS-S method, five times more M6 was produced. In both methods, the time to maximum concentration for morphine metabolites was 20-40 minutes, much shorter than expected from oral, intranasal, or intravenous administration. The study shows that the method of inhalation may have a profound effect on the pharmacokinetics of morphine. It is possible that the lungs metabolize morphine to glucuronides themselves and in different proportions from those seen after systemic administration. The BCTS-S method was found to be potentially superior to the BCTS-MC method in local action in the lungs.

[Development of a method for determining antidepressant drugs in nails and its usefulness in forensic toxicology]. / Opracowanie metody oznaczania leków przeciwdepresyjnych w paznokciach i jej wykorzystanie w toksykologii sadowej.

The report presents the possibility of using alternative material in determinations of antidepressants taking as exemplified by flupentixol. At the first stage of the study, the method of flupentixol isolation from nails and its identification were elaborated. Determinations were performed in fingernail/toenail samples originating from individuals who had been administered flupentixol in therapeutic doses for at least 12 months before sample collection. The nails were obtained 4, 6, 7, 8 and 10 months after discontinuing the drug administration. The determinations were made by liquid chromatography coupled with electrospray-ionization mass spectrophotometry (LC-ESI-MS). The study showed that 4 months after discontinuing the drug, the nail flupentixol concentration was within the range of 0.086-0.109 ng/mg, after 6 months, the drug level was 0.036-0.042 ng/mg, after 7 months, it was 0.018-0.021 ng/mg and after 8 months - 0.020-0.022 ng/mg. Ten months after discontinuation of therapy, flupentixol was no longer found in nails.

[Application of liquid chromatography coupled with mass spectrometry (LC/MS) to determine antidepressants in blood samples]. / Wykorzystanie chromatografii cieczowej z detektorem masowym (LC/MS) do oznaczania leków przeciwdepresyjnych we krwi.

A simultaneous determination of twelve antidepressant drugs (amitriptyline, chlorpromazine, clomipramine, doxepin, fluoxetine, levomepromazine, maprotiline, paroxetine, perazine, promazine, sertraline, thioridazine) in blood samples was developed using high-performance liquid chromatography with mass spectrometry (LC/MS). Blood samples were extracted with acetonitrile and separated by HPLC on a reversed phase C18 column with a mobile phase consisting of acetonitrile -0.1% trifluoroacetic acid (50:50 (v/v) at a flow-rate of 0.4 ml/min. The analytes were determined using electrospray ionization in a single quadrupole mass spectrometer. LC-ESI-MS was performed in the selected-ion monitoring (SIM) mode using target ions. The validated method was successfully used to analyze antidepressants in blood samples collected from four victims of suicide by hanging.

[Determination of antidepressants in biological materials originating from victims of suicide by hanging]. / Oznaczanie leków przeciwdepresyjnych w materiale biologicznym pobranym od osób, których zgon byl skutkiem samobójstwa przez powieszenie.

The report presents the results of determinations of medication levels in biological materials collected from victims of suicide by hanging. The analysis included cases autopsied at Forensic Medicine Department in Bydgoszcz in the years 2005-2006. The authors observed that of 928 postmortem examinations, suicide by hanging accounted for 7.8% of cases; in this group, 11.1% victims were female and 88.9% were male. The most numerous group included individuals aged 20-29 years (20.7%), while the smallest group consisted of suicide victims below 20 years of age (8.3%). A total of 23.6% of individuals were under the influence of antidepressant drugs at the moment of death. The detected antidepressants included phenotiazine derivatives and such tricyclic antidepressants as amitryptyline, chloropromazine, clomipramine, levomepromazine, mianserin, promazine and thioridazine. Based on the above investigations, 11.1% of suicide victims may be said to have taken antidepressants in the past, but to be under no influence of such medications at the time of death.

[Determination of bromochlorodifluoromethane (Halon 1211) in biological material by gas chromatography with mass detector]. / Oznaczanie bromochlorodifluorometanu (Halon 1211) w materiale biologicznym metoda chromatografii gazowej z detektorem masowym (GC/MS).

A gas chromatographic method with mass spectrometry has been developed for the determination of bromochlorodifluoromethane (Halon 1211) in biological material (whole blood, organ samples). After incubation of the sample (temp. 65 degrees C, 15 min), 10 microliters of the headspace is analysed using a capillary column DB-5 ms (30 m x 0.25 mm x 0.25 micron). Quantitative analysis was made with the use of a single ion monitoring option--m/z 85 and m/z 87. This developed method was used to determine the concentration of bromochlorodifluoromethane in biological material collected from the body of the man whose death was due to intoxication of Halon 1211--fire-extinguisher contents.