Interpretation of melperone intoxication: post-mortem concentration distribution and interpretation of intoxication data

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Marek Dziadosz ◽  
Katarina Bolte ◽  
Wolfgang Rosenberger ◽  
Michael Klintschar ◽  
Jörg Teske

Abstract Objectives Since melperone abuse with lethal intoxication is common, expert opinions based on therapeutical and lethal concentration ranges can be considered as important. Because there is a lack of information about fatalities caused by melperone mono-intoxications and data on tissue samples with concentration distribution, the aim of this work is the examination of lethal concentration ranges of melperone and drug quantification in different matrices. Methods An LC-MS/MS method was applied for analyses performed in blood and tissue samples. Quantification based on standard addition and sample preparation on liquid–liquid extraction with 1-chlorobutane. An appropriate tissue homogenization was performed ahead of extraction with an IKA Ultra-Turrax-Tube-Drive®. A Luna 5 µm C18 (2) 100 Å, 150  × 2 mm analytical column was used for chromatographic separation and the elution was performed with two mobile phases consisted of A (H2O/methanol = 95/5, v/v) and B (H2O/methanol = 3/97, v/v) both with 10 mM ammonium acetate and 0.1% acetic acid. Results A multi-drug LC-MS/MS analytical method developed was applied successfully for melperone quantification in different post-mortem matrices. No analytical problems could be identified during method development and analyses of real samples. The melperone lethal concentration calculated in femoral blood of the drug mono-intoxication investigated was 10 mg/L. Melperone concentration distribution was presented for the first time. Conclusions The lethal reference concentration of melperone in femoral blood of 17.1 mg/L pointed out in different reference lists should be used with caution. Instead, a lower lethal melperone concentration should be considered. The post-mortem concentration distribution of the drug presented could be helpful in the interpretation of cases where no blood samples are available.

2021 ◽  
Vol 36 (3) ◽  
pp. 233-237
Author(s):  
Marek Dziadosz ◽  
Katarina Bolte ◽  
Wolfgang Rosenberger ◽  
Michael Klintschar ◽  
Jörg Teske

Abstract Objectives Since melperone abuse with lethal intoxication is common, expert opinions based on therapeutical and lethal concentration ranges can be considered as important. Because there is a lack of information about fatalities caused by melperone mono-intoxications and data on tissue samples with concentration distribution, the aim of this work is the examination of lethal concentration ranges of melperone and drug quantification in different matrices. Methods An LC-MS/MS method was applied for analyses performed in blood and tissue samples. Quantification based on standard addition and sample preparation on liquid–liquid extraction with 1-chlorobutane. An appropriate tissue homogenization was performed ahead of extraction with an IKA Ultra-Turrax-Tube-Drive®. A Luna 5 µm C18 (2) 100 Å, 150  × 2 mm analytical column was used for chromatographic separation and the elution was performed with two mobile phases consisted of A (H2O/methanol = 95/5, v/v) and B (H2O/methanol = 3/97, v/v) both with 10 mM ammonium acetate and 0.1% acetic acid. Results A multi-drug LC-MS/MS analytical method developed was applied successfully for melperone quantification in different post-mortem matrices. No analytical problems could be identified during method development and analyses of real samples. The melperone lethal concentration calculated in femoral blood of the drug mono-intoxication investigated was 10 mg/L. Melperone concentration distribution was presented for the first time. Conclusions The lethal reference concentration of melperone in femoral blood of 17.1 mg/L pointed out in different reference lists should be used with caution. Instead, a lower lethal melperone concentration should be considered. The post-mortem concentration distribution of the drug presented could be helpful in the interpretation of cases where no blood samples are available.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Charlene Clarke ◽  
Katrin Smith ◽  
Samantha J. Goldswain ◽  
Christopher Helm ◽  
David V. Cooper ◽  
...  

AbstractMycobacterium bovis is the causative agent of bovine tuberculosis (bTB) in wildlife. Confirmation of M. bovis infection relies on mycobacterial culture, which is time-consuming. Collection and transportation of infectious material also pose a human health risk. PrimeStore Molecular Transport Medium (MTM) has been shown to effectively inactivate infectious organisms, making it a safe method for handling infectious samples. This study investigated an in-field sampling technique for rapid, safe detection of M. bovis in buffalo tissues. Potentially infected tissues from bTB test-positive buffaloes were swabbed at post-mortem examination and stored in PrimeStore MTM at ambient temperature until Xpert MTB/RIF Ultra testing was performed. Additionally, tissue samples were frozen and transported before homogenisation for culture and Ultra testing. Oral swabs were collected from M. bovis-unexposed buffaloes as a negative control cohort. Mycobacterium tuberculosis complex (MTBC) DNA was detected by Ultra in 13/16 tissue swabs and 9/16 matched tissue homogenates from culture-confirmed M. bovis-positive buffalo tissues. MTBC DNA was not detected in swabs from M. bovis-unexposed animals, showing the potentially high specificity of Ultra with PrimeStore swabs. PrimeStore MTM sample processing, in combination with the Ultra assay, has the potential to provide a safe, rapid post-mortem screening test for M. bovis in buffaloes.


Author(s):  
Linda Zoungrana ◽  
Alyssa N. Smith ◽  
M. Cecilia do Nascimento Nunes

Method development and optimization play a central role in analytical chemistry and more specifically in food biochemistry. When it comes to research, it is common that analytical methods need to be modified to specific experimental biological tissues. While there are several published works on the activity of the enzyme chalcone synthase (CHS) in plant materials, such as sweet basil using ultra- high-performance liquid chromatography, there is a lack of information regarding extraction and activity of CHS in strawberries. Therefore, the main objective of this work was to optimize existing published methods for extraction and activity of CHS in strawberries, using spectrophotometric analysis. It was done through a literature search, a method dissection was performed, followed by theoretical optimization of the protocol, and finally an experimental optimization


Xenobiotica ◽  
1976 ◽  
Vol 6 (5) ◽  
pp. 275-280 ◽  
Author(s):  
John Caldwell ◽  
John R. Moffatt ◽  
Robert L. Smith

Viruses ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 649 ◽  
Author(s):  
Yale ◽  
Gibson ◽  
Mani ◽  
P.K. ◽  
Costa ◽  
...  

Rabies is a fatal zoonotic disease transmitted by the bite of a rabid animal. More than 95% of the human rabies cases in India are attributed to exposure to rabid dogs. This study evaluated the utility of a lateral flow immunochromatographic assay (LFA) (Anigen Rapid Rabies Ag Test Kit, Bionote, Hwaseong-si, Korea) for rapid post mortem diagnosis of rabies in dogs. Brain tissue was collected from 202 animals that were screened through the Government of Goa rabies surveillance system. The brain tissue samples were obtained from 188 dogs, nine cats, three bovines, one jackal and one monkey. In addition, 10 dogs that died due to trauma from road accidents were included as negative controls for the study. The diagnostic performance of LFA was evaluated using results from direct fluorescence antibody test (dFT); the current gold standard post mortem test for rabies infection. Three samples were removed from the analysis as they were autolysed and not fit for testing by dFT. Of the 209 samples tested, 117 tested positive by LFA and 92 tested negative, while 121 tested positive by dFT and 88 tested negative. Estimates of LFA sensitivity and specificity were 0.96 (95% CI 0.91–0.99) and 0.99 (95% CI 0.94–1.00), respectively. The LFA is a simple and low-cost assay that aids in the rapid diagnosis of rabies in the field without the need for expensive laboratory equipment or technical expertise. This study found that Bionote LFA has potential as a screening tool in rabies endemic countries.


2020 ◽  
pp. 002580242097381
Author(s):  
Laura J Hikin ◽  
Paul R Smith ◽  
Peter D Maskell ◽  
Hassan Kurimbokus ◽  
Emily Ashong ◽  
...  

Etizolam is a thienodiazepine that although licensed for clinical usage in Japan, India and South Korea is commonly abused and detected in post-mortem cases around the world. To date, there are limited data in the literature to allow for the interpretation of blood concentrations of etizolam in post-mortem cases. A liquid chromatography with tandem mass spectrometry method was used to quantitate etizolam concentrations in 28 post-mortem cases where etizolam was detected. The median concentration of etizolam in femoral blood was 8.5 ng/mL (range 1.0–172.0 ng/mL; n = 24); in antemortem plasma, the etizolam concentration range was 4–44 ng/mL ( n = 4). The mean age of the individuals abusing etizolam was 38.5 ± 8.4 years (median 39 years), with the majority being male (86%). In all of the cases, multiple drugs were detected, with the most common being pregabalin (61%) followed by morphine/heroin (54%), diazepam (54%) and benzoylecgonine (21%), illustrating the increasing problem of poly-substance use in drug abusers. The cause of death in the cases in which etizolam was detected was multi-drug toxicity in 87.5% of the cases, with 12.5% unrelated to drug use (hangings and blunt-force trauma). These data will further help forensic practitioners with the interpretation of post-mortem etizolam concentrations.


2011 ◽  
Vol 94 (4) ◽  
pp. 1026-1033 ◽  
Author(s):  
Phil E Johnson ◽  
Sabine Baumgartner ◽  
Thomas Aldick ◽  
Conrad Bessant ◽  
Valeria Giosafatto ◽  
...  

Abstract Allergen detection and quantification is an essential part of allergen management as practiced by food manufacturers. Recently, protein MS methods (in particular, multiple reaction monitoring experiments) have begun to be adopted by the allergen detection community to provide an alternative technique to ELISA and PCR methods. MS analysis of proteins in foods provides additional challenges to the analyst, both in terms of experimental design and methodology: (1) choice of analyte, including multiplexing to simultaneously detect several biologically relevant molecules able to trigger allergic reactions; (2) choice of processing stable peptide markers for different target analytes that should be placed in publicly available databases; (3) markers allowing quantification (e.g., through standard addition or isotopically labeled peptide standards); (4) optimization of protease digestion protocols to ensure reproducible and robust method development; and (5) effective validation of methods and harmonization of results through the use of naturally incurred reference materials spanning several types of food matrix.


2020 ◽  
Vol 9 (7) ◽  
pp. 394-401
Author(s):  
Sophie A. Blirup-Plum ◽  
Thomas Bjarnsholt ◽  
Henrik E. Jensen ◽  
Kasper N. Kragh ◽  
Bent Aalbæk ◽  
...  

Aims CERAMENT|G is an absorbable gentamicin-loaded biocomposite used as an on-site vehicle of antimicrobials for the treatment of chronic osteomyelitis. The purpose of the present study was to investigate the sole effect of CERAMENT|G, i.e. without additional systemic antimicrobial therapy, in relation to a limited or extensive debridement of osteomyelitis lesions in a porcine model. Methods Osteomyelitis was induced in nine pigs by inoculation of 104 colony-forming units (CFUs) of Staphylococcus aureus into a drill hole in the right tibia. After one week, the pigs were allocated into three groups. Group A (n = 3) received no treatment during the study period (19 days). Groups B (n = 3) and C (n = 3) received limited or extensive debridement seven days postinoculation, respectively, followed by injection of CERAMENT|G into the bone voids. The pigs were euthanized ten (Group C) and 12 (Group B) days after the intervention. Results All animals presented confirmatory signs of bone infection post-mortem. The estimated amount of inflammation was substantially greater in Groups A and B compared to Group C. In both Groups B and C, peptide nucleic acid fluorescence in situ hybridization (PNA FISH) of CERAMENT|G and surrounding bone tissue revealed bacteria embedded in an opaque matrix, i.e. within biofilm. In addition, in Group C, the maximal measured post-mortem gentamicin concentrations in CERAMENT|G and surrounding bone tissue samples were 16.6 μg/ml and 6.2 μg/ml, respectively. Conclusion The present study demonstrates that CERAMENT|G cannot be used as a standalone alternative to extensive debridement or be used without the addition of systemic antimicrobials. Cite this article: Bone Joint Res 2020;9(7):394–401.


2007 ◽  
Vol 170 (2-3) ◽  
pp. 193-199 ◽  
Author(s):  
Frank Sporkert ◽  
Marc Augsburger ◽  
Christian Giroud ◽  
Clarisse Brossard ◽  
Chin B. Eap ◽  
...  

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