Determination of ramipril in human plasma and study of its fragmentation by UPLC-Q-TOF-MS with positive electrospray ionization

This report presents the application of ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry with positive electrospray ionization, to determine ramipril in human plasma. First, the proteins in human plasma were precipitated using acetonitrile, then the supernatant was extracted by ethyl acetate at pH 3 and, finally, the extract was analyzed using a UPLC-Q-TOF-MS system. The method was validated and the coefficient of determination (R2) was > 0.999, the lower limit of quantification (LLOQ) was 0.5 ng mL–1. Precision, recovery and stability were determined for three different concentrations of ramipril. RSD for this method ranged from 3.3 to 8.6 %. The intra-day mean recovery was from 65.3 to 97.3 %. In addition, the fragmentation of ramipril was studied. Due to high resolution of the spectrometer, it was possible to measure fragment masses accurately and determine their molecular and chemical formulas with high accuracy

Technical note: Residues of gaseous air pollutants in rabbit (Oryctolagus cuniculus) tissues

[EN] The modern consumer is concerned not only for meat quality, but also about animal welfare and the environment. Studies were conducted to determine the concentration of gaseous residues in the tissues of rabbits. For this purpose, gaseous air pollutants were measured at the height of rabbit cages. Immediately after slaughter, samples were taken for analysis to determine the level of residual pollutants in the tissues (blood, perirenal fat and lung). Headspace gas chromatography was performed on the tissue samples to test for volatile toxic substances. Gas residues of 11 compounds were determined in the samples of blood, perirenal fat and lungs. The same chemicals were present in the air of the farm and the animal tissues, which may indicate their capacity for bioaccumulation. 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Washington, U.S.Geller I., Hartmann R.J., Randle S.R., Gause E.M. 1979. Effects of acetone and toluene vapors on multiple schedule performance of rats. Pharmacol. Biochem. Behav., 11: 395-399. https://doi.org/10.1016/0091-3057(79)90114-XGugołek A., Juśkiewicz J., Strychalski J., Zwoliński C, Żary-Sikorska E., Konstantynowicz M. 2017. The effects of rapeseed meal and legume seeds as substitutes for soybean meal on productivity and gastrointestinal function in rabbits. Arch. Anim. Nutr., 71: 311-326. https://doi.org/10.1080/1745039X.2017.1322796Howard P.H. 1989. Handbook of environmental fate and exposure data for organic chemicals. Volume 1: Large production and priority pollutants. Lewis Publishers Inc., Chelsea, Michigan.Huff, J., Chan, P., Melnick, R. 2010. Clarifying carcinogenicity of ethylbenzene. Regul. Toxicol. Pharmacol., 58: 167-169. https://doi.org/10.1016/j.yrtph.2010.08.011Kawai T., Yasugi T., Mizunuma K., Horiguchi S., Iguchi H., Ikeda M. 1992. Curvi-linear relation between acetone in breathing zone air and acetone in urine among workers exposed to acetone vapor. Toxicol. Lett. 62: 85-91. https://doi.org/10.1016/0378-4274(92)90081-TKonéab A.P., Desjardinsbc Y., Gosselinbc A., Cinq-Marsa D., Guaya F., Saucier L. 2019. Plant extracts and essential oil product as feed additives to control rabbit meat microbial quality. Meat Sci., 50: 111-121. https://doi.org/10.1016/j.meatsci.2018.12.013Lauwerys, R., Bernard, A., Viau, C., Buchet, J.P. 1985. Kidney disorders and hematotoxicity from organic solvent exposure. Scand. J. Work Environ. Health., 11 Suppl 1: 83-90. https://doi.org/10.5271/sjweh.2238Michl R., Hoy St. 1996. Results of continuous measuring of gases in rabbit keeping by using multigas-monitoring. Berl. Munch. Tierarztl. Wochenschr., 109: 340-343.Nowakowicz-Dębek B., Buszewicz G., Chmielowiec-Korzeniowska A., Saba L., Bis-Wencel H., Wnuk W. 2007. Residues of volatile gaseous substances in the tissues of polar foxes. Med. Wet., 63: 688-691.Nowakowicz-Dębek B., Łopuszyński W. 2004. Effects, of air pollution on changes in the polar fox (Alopex lagopus) organism. Med. Wet., 60: 845-848.OECD SIDS. 2002. Ethylbenzene: SIDS Initial Assessment Report For SIAM 14. Paris, France: UNEP Publications 7, 1-177.Ogata M., Fujisawa K., Ogino Y., Mano E. 1984. Partition coefficients as a measure of bioconcentration potential of crude oil compounds in fish and shellfish. Bull. Environ. Contam. Toxicol., 33: 561-567. https://doi.org/10.1007/BF01625584Peckham, T., Kopstein, M., Klein, J., Dahlgren, J. 2014. Benzenecontaminated toluene and acute myeloid leukemia: a case series and review of literature. Toxicol. Ind. Health., 30: 73-81. https://doi.org/10.1177/0748233712451764Plaa G.L., Hewitt W.R., Du Souich P., Caille G., Lock S. 1982. Isopropanol and acetone potentiation of carbon tetrachloride-induced hepatotoxicity: single versus repetitive pretreatments in rats. J. Toxicol. Environ. Health., 9: 235-250. https://doi.org/10.1080/15287398209530158Rommers, J.M., de Jong, I.C., de Greef, K.H. 2015. The development of a welfare assessment protocol for commercially housed rabbits. In 19th International symposium on housing and diseases of rabbits, furbearing animals and pet animals, 27-28 May 2015, Celle, Germany.Saghir, S.A., Rick, D.L., McClymont, E.L., Zhang, F., Bartels, M.J., Bus, J.S. 2009. Mechanism of ethylbenzene-induced mousespecific lung tumor: metabolism of ethylbenzene by rat, mouse, and human liver and lung microsomes. Toxicol. Sci., 107: 352-366. https://doi.org/10.1093/toxsci/kfn244Scholl H.R., Iba M.M. 1997. Pharmacokinetics of and CYP1A induction by pyridine and acetone in the rat: interactions and effects of route of exposure. Xenobiotica, 27: 265-277. https://doi.org/10.1080/004982597240596Tang W., Hemm I., Eisenbrand G. 2000. Estimation of human exposure to styrene and ethylbenzene. 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COVID-19: Specific and Non-Specific Clinical Manifestations and Symptoms: The Current State of Knowledge

Coronavirus disease 2019 (COVID-19), due to the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has become an epidemiological threat and a worldwide concern. SARS-CoV-2 has spread to 210 countries worldwide and more than 6,500,000 confirmed cases and 384,643 deaths have been reported, while the number of both confirmed and fatal cases is continually increasing. COVID-19 is a viral disease that can affect every age group-from infants to the elderly-resulting in a wide spectrum of various clinical manifestations. COVID-19 might present different degrees of severity-from mild or even asymptomatic carriers, even to fatal cases. The most common complications include pneumonia and acute respiratory distress syndrome. Fever, dry cough, muscle weakness, and chest pain are the most prevalent and typical symptoms of COVID-19. However, patients might also present atypical symptoms that can occur alone, which might indicate the possible SARS-CoV-2 infection. The aim of this paper is to review and summarize all of the findings regarding clinical manifestations of COVID-19 patients, which include respiratory, neurological, olfactory and gustatory, gastrointestinal, ophthalmic, dermatological, cardiac, and rheumatologic manifestations, as well as specific symptoms in pediatric patients

Evidence for cytoprotective effect of carbon monoxide donor in the development of acute esophagitis leading to acute esophageal epithelium lesions

Exposure to acidic gastric content due to malfunction of lower esophageal sphincter leads to acute reflux esophagitis (RE) leading to disruption of esophageal epithelial cells. Carbon monoxide (CO) produced by heme oxygenase (HMOX) activity or released from its donor, tricarbonyldichlororuthenium (II) dimer (CORM-2) was reported to protect gastric mucosa against acid-dependent non-steroidal anti-inflammatory drug-induced damage. Thus, we aimed to investigate if CO affects RE-induced esophageal epithelium lesions development. RE induced in Wistar rats by the ligation of a junction between pylorus and forestomach were pretreated i.g. with vehicle CORM-2; RuCl3; zinc protoporphyrin IX, or hemin. CORM-2 was combined with NG-nitro-L-arginine (L-NNA), indomethacin, capsazepine, or capsaicin-induced sensory nerve ablation. Esophageal lesion score (ELS), esophageal blood flow (EBF), and mucus production were determined by planimetry, laser flowmetry, histology. Esophageal Nrf-2, HMOXs, COXs, NOSs, TNF-α and its receptor, IL-1 family and IL-1 receptor antagonist (RA), NF-κB, HIF-1α, annexin-A1, suppressor of cytokine signaling (SOCS3), TRPV1, c-Jun, c-Fos mRNA/protein expressions, PGE2, 8-hydroxy-deoxyguanozine (8-OHdG) and serum COHb, TGF-β1, TGF-β2, IL-1β, and IL-6 content were assessed by PCR, immunoblotting, immunohistochemistry, gas chromatography, ELISA or Luminex platform. Hemin or CORM-2 alone or combined with L-NNA or indomethacin decreased ELS. Capsazepine or capsaicin-induced denervation reversed CORM-2 effects. COHb blood content, esophageal HMOX-1, Nrf-2, TRPV1 protein, annexin-A1, HIF-1α, IL-1 family, NF-κB, c-Jun, c-Fos, SOCS3 mRNA expressions, and 8-OHdG levels were elevated while PGE2 concentration was decreased after RE. CO donor-maintained elevated mucosal TRPV1 protein, HIF-1 α, annexin-A1, IL-1RA, SOCS3 mRNA expression, or TGF-β serum content, decreasing 8-OHdG level, and particular inflammatory markers expression/concentration. CORM-2 and Nrf-2/HMOX-1/CO pathway prevent esophageal mucosa against RE-induced lesions, DNA oxidation, and inflammatory response involving HIF-1α, annexin-A1, SOCS3, IL-1RA, TGF-β-modulated pathways. Esophagoprotective and hyperemic CO effects are in part mediated by afferent sensory neurons and TRPV1 receptors activity with questionable COX/PGE2 or NO/NOS systems involvement

Medico-legal and legal-penal aspects of expert opinions and adjudication in cases of intoxications with intoxicating agents and ethanol-like intoxicants

Introduction: The available legal regulations in Poland do not define the concentration thresholds enabling to differentiate between the states of “after-use” versus “under the influence” of a drug, as it is in the case of alcohol. The aim of the study was to analyse jurisdiction in cases regarding the evaluation of the effects of intoxicating agents and ethanol-like intoxicants and to identify ambiguities and gaps in the applicable regulations leading to problems in preparing expert opinions. Material and methods: The material included the opinions of experts in the field of toxicology and forensic medicine made by the Department of Forensic Medicine in Lublin in the years 2009–2011 and records obtained in the process of inquiry from the regional prosecutor’s offices and courts in 52 cases. Results : Amongst 52 cases in which the ordered toxicology examinations demonstrated the presence of intoxicating agents in drivers’ blood (tetrahydrocannabinols in 39 and amphetamine in 21 cases) in 2 cases petty offence proceedings were instituted (Art. 87 of the Petty Offence Code) although high concentrations of xenobiotics indicated the state of being “under the influence” of a narcotic drug (Art. 178a of the Penal Code). Three cases were discontinued despite expert opinions that the drivers were at least in the after-narcotic use state. In only 3 cases were witnesses asked to provide testimony about the circumstances of the driver’s conduct. Conclusions : The analysis has demonstrated that judicial bodies expect forensic expertise based exclusively on toxicological examination results; when expert findings are inconclusive, they only administer litigations opportunistically applying the principle of the presumption of innocence understood literally. Considering the above, threshold values of “use” and “influence” of the most commonly detected drugs should be urgently determined

Determination of Cyanide in Blood for Forensic Toxicology Purposes—A Novel Nci Gc-Ms/Ms Technique

One of the recently evolving methods for cyanide determination in body fluids is GC-MS, following extractive alkylation with pentafluorobenzyl bromide or pentafluorobenzyl p-toluenesulfonate. The aim of this study was to improve previous GC methods by utilizing a triple quadrupole mass spectrometer, which could enhance selectivity and sensitivity allowing for the reliable confirmation of cyanide exposure in toxicological studies. Another purpose of this study was to facilitate a case investigation including a determination of cyanide in blood and to use the obtained data to confirm the ingestion of a substance, found together with a human corpse at the forensic scene. The blood samples were prepared following extractive alkylation with a phase transfer catalyst tetrabutylammonium sulfate and the PFB-Br derivatization agent. Optimal parameters for detection, including ionization type and multiple reaction monitoring (MRM) transitions had been investigated and then selected. The validation parameters for the above method were as follows—linear regression R2 = 0.9997 in the range of 0.1 µg/mL to 10 µg/mL; LOD = 24 ng/mL; LOQ = 80 ng/mL and an average recovery of extraction of 98%. Our study demonstrates the first attempt of cyanide determination in blood with gas chromatography-tandem mass spectrometry. The established method could be applied in forensic studies due to MS/MS confirmation of organic cyanide derivative and low matrix interferences owning to utilizing negative chemical ionization