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Fluvoxamine is a selective serotonin reuptake inhibitor, with a half-life of about 30 hours, that is commonly prescribed in the treatment of depression and obsessive and compulsive disorders. Though its more favorable adverse effect profile in comparison to tricyclic antidepressants, overdosages could lead to severe central nervous system depression. We hereby report the case of a 48-year-old woman with psychiatric disorders, who died in the Protected Community where she lived. An autopsy, during which multiorgan congestion and aspiration of gastric content were found, was performed 9 days after the death. Femoral and cardiac blood, urine and bile were collected for toxicological analysis. GC-MS, LC-MS-MS and LC-HRMS screenings were performed on blood samples. The analysis allowed to identify the following drugs: fluvoxamine, clotiapine, 7-aminoclonazepam, propranolol, gabapentin and haloperidol. Quantification of the detected drugs in blood was performed by means of a validated LC-MS-MS analytical procedure, and the following results were achieved: fluvoxamine (2.20 mg/L), gabapentin (41.00 mg/L), 7-aminoclonazepam (0.24 mg/L), clotiapine (0.07 mg/L), haloperidol (<0.01 mg/L) and propranolol (0.24 mg/L). Fluvoxamine concentration in blood exceeded ~10 times the upper limit of therapeutic blood levels (0.23 mg/L). Contributory causes of death, such as due to multiple drug use, however, cannot be excluded. The distribution of fluvoxamine in all biological fluids was evaluated and a postmortem redistribution effect was observed (C/P blood ratio: 1.86). Fluvoxamine acid metabolite was identified in urine, bile and in cardiac blood, through an LC-QTOF analytical procedure., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

We report the analysis of the synthetic cathinones α-pyrrolidinohexiophenone (α-PHP) and α-pyrrolidinopentiophenone (α-PVP), both pyrovalerone derivatives, in blood, urine, gastric contents, main tissues and hair of a deceased person. Qualitative and quantitative analyses were performed by LC-MS-MS. All the biological samples were collected during autopsy and extracted/purified onto a solid phase extraction cartridge before instrumental analysis. The method was validated for blood and urine and proved to be highly sensitive and specific for both the synthetic cathinones (limit of detection: 0.2 ng/mL and limit of quantification: 0.5 ng/mL). Analyses provided negative results for α-PVP in all biological samples except for the 2-cm proximal hair segment, confirming that the young man had consumed in the last 2 months this compound; instead hair analysis proved that the man was a heavy α-PHP user. α-PHP was identified and quantified in biological fluids and tissues. Interestingly, bile and urine concentrations (1.2 and 5.6 ng/mL, respectively) were fairly lower than blood collected into the thoracic cavity (15.3 ng/mL). The highest concentrations were measured for lung (71.1 ng/mL) and spleen (83.8 ng/mL). Concentrations of 3.5, 7.9, 4.7 and 23.6 ng/mL were measured in liver, kidney, brain and heart, respectively. Even if it is not possible to evaluate the presence of this drug in biological samples as a cause of death, to our knowledge, this is the first case of α-PHP finding in postmortem samples, and its potential toxic effects should be elucidated in the future.

A liquid chromatographic tandem mass spectrometric method for the identification and quantification of 18 cardiovascular drugs was developed in order to evaluate two cases of fatal intoxication involving diltiazem and amlodipine respectively. Samples were simply diluted and centrifuged using a three-steps procedure with methanol, acetonitrile and mobile phase. The method proved to be selective and all the validation parameters fulfilled the acceptance criteria. In particular, linearity was studied in the range limits of quantitation (LOQ)-1,000 ng/mL (LOQ ranging from 0.8 to 33.3 ng/mL for urine and from 0.7 to 41.3 ng/mL for whole blood). The method was successfully applied to two real cases involving diltiazem and amlodipine fatal intoxications, respectively. Though the subject intoxicated by diltiazem did survive several hours after drug intake, central and peripheral blood levels at autopsy were extremely high (23.4 and 13.4 mg/L, respectively); the cause could be due to the formation of a pharmacobezoar that was found in the duodenum and that could have delayed the drug absorption. Moreover, diltiazem showed postmortem redistribution. On the contrary, the amlodipine peripheral blood level in the second case was relatively low (0.17 mg/L), thus confirming that even the uncontrolled intake of a less toxic calcium channel blocker can lead to death. Furthermore, blood samples were analyzed after 2 years of storage at -20°C: both diltiazem and amlodipine showed a significant degradation (70 and 99%, respectively).

In postmortem cases, detection of drugs in blood is most relevant with regard to determining cause of death. However, it is sometimes also of interest to gain as much information as possible regarding the deceased's use of drugs in the period before death. The aim of this study was to compare results from analyses of a repertoire of psychoactive medicinal drugs in blood and hair samples from a larger material of postmortem cases. Hair samples in addition to blood were collected from 55 forensic autopsies and analyzed for a repertoire of 39 medicinal drugs (benzodiazepines, antidepressants and antipsychotics) using av fully validated liquid chromatography-tandem mass spectrometry method. In total, hair analyses gave information of the use of drugs not detected in blood in 47 of the 55 cases (85%). The most frequent single drugs detected in hair, but absent in blood, were benzodiazepines (64%), followed by antidepressants (35%). In each case, 1-10 (median two) single drugs were detected in hair, but absent in blood. In only two cases (4%), benzodiazepines were detected in blood and no benzodiazepines were detected in hair. In conclusion, hair analyses in addition to blood frequently indicate prior use of drugs that could yield important information about for instance unknown psychiatric diagnoses. In only a small number of cases lack of detections from the same drug class in hair might indicate reduced tolerance to drug effects.

Ethyl glucuronide (EtG) and ethyl sulfate (EtS) are specific and sensitive biomarkers for the diagnosis of acute or chronic alcohol abuse. Due to postmortem alcohol production in biological tissues, they have recently been evaluated as potential biomarkers of ethanol ingestion. This in vitro study aimed to evaluate all developmental stages of the fly Calliphora vicina L. (Calliphoridae). Different pig substrates were used during the in vitro experiments to rear C. vicina Experiments were performed to: (i) assess the presence of EtG and EtS in larvae, pupae and insects; (ii) study variability due to the substrates characteristics; (iii) evaluate the possibility of false positives due to external alcohol contamination; and (iv) estimate the potential metabolism of ethanol by the insects. EtS was found in all of the samples where the standard was added to the substrate. Muscle provided the most reliable results. EtS was found in larvae, pupae and puparia. EtG and EtS were found in larvae and pupae collected from the body of an alcoholic found dead in his home. This study showed that maggots, pupae and puparia could be a useful matrix for the evaluation of antemortem alcohol ingestion., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Tanax is a veterinary formulation for euthanasia comprising embutramide, mebezonium iodide and tetracaine. A 37-year-old female was found dead on her bed, with three empty used syringes and a bottle of Tanax beside her body. Three needle puncture marks were observed on the body. The aim of this study was to evaluate the distribution of embutramide and mebezonium iodide in different biological matrices (femoral and cardiac blood, liver, muscle and vitreous humor) using a chromatographic method for the simultaneous determination of the two drugs. A direct and sensitive liquid chromatography-tandem mass spectrometry method was developed in multiple reaction monitoring mode with positive ionization. Lidocaine was used as an internal standard. Limits of detection and quantitation of 0.01 and 0.05 mg/L, respectively, were reached for both compounds. Embutramide levels ranged from 2.74 mg/L in vitreous humor to 5.06 mg/L in femoral blood, while mebezonium iodide was found at widely differing concentrations (ranging from 2.80 mg/kg in muscle to 24.80 mg/kg in liver). The chromatographic method developed for this study provides a very simple and sensitive means for the simultaneous determination of embutramide and mebezonium iodide, the emetic concentrations of which were consistent with suicides reported in the literature.

Serum/blood (S/B) concentration ratios for ethyl glucuronide (EtG) and ethyl sulfate (EtS) are missing from the literature, and the aim of this study was to determine these ratios in samples from patients at admission to an alcohol rehabilitation clinic. Two blood samples were collected simultaneously, and EtG and EtS were analyzed in whole blood and serum, respectively, using a liquid chromatography-mass spectrometry method. Separate calibration standards were prepared in both whole blood and serum for the calculation of whole blood and serum concentrations, respectively. Thirteen pairs of serum and whole blood were analyzed. The median S/B value for EtG was 1.69, and the range was 1.33-1.90. For EtS, the median S/B ratio was 1.30, and the range was 1.08-1.47. The S/B ratio was significantly lower for EtS than for EtG (p < 0.001). The higher concentrations of EtG and EtS in serum than in whole blood have to be considered when whole blood results obtained from forensic toxicology are compared to serum or plasma results from clinical laboratories.