Fatal Suicidal Intoxication with Pentoxifylline Complicated by Cardiovascular Disorders.

Pentoxifylline is a xanthine derivative used in vascular disorders that is recognized as a safe drug for patients. The paper describes a rare case of fatal and suicidal pentoxifylline poisoning in an 82-year-old man with multiple preexisting diseases (arterial hypertension, coronary artery disease, type 2 diabetes, and intermittent claudication). The patient was admitted to the clinical toxicology unit approximately 2 h after the overdose and died 36 h after the admission despite intensive care. Multiple arterial blood gas analyses and other laboratory tests were performed during the hospitalization and are reported in the paper. Postmortem examination of the biological material was carried out with the use of histopathological techniques. The toxicological studies using chromatographic techniques coupled with mass spectrometry showed that postmortem blood levels of pentoxifylline have been found in the range which is described in the available literature to be toxic and lethal. The analysis of test results and clinical data showed that the patient died as a result of increasing circulatory and respiratory failure, complicated by disorders of the acid-base and electrolyte balance (respiratory alkalosis, concomitant lactic acidosis, and hypokalemia), hyperglycemia, and coagulation disorders.

Fatal N-Ethylhexedrone Intoxication.

N-Ethylhexedrone [2-(ethyloamino)-1-phenylhexan-1-one; α-ethylaminohexanophenone (NEH)] is one of the most recent synthetic cathinones that appeared on the illegal market in late 2015. The majority of information concerning the model of consumption of NEH and its impact on the body originates only from self-reports from gray literature websites and drug forums. There are only limited data associated with the concentrations of NEH in blood samples available in the literature. This article presents a case of fatal NEH intoxication and a method for the determination of this substance in whole blood. A 21-year-old man without any diagnosed diseases was admitted to the hospital due to disorientation, aggression and finally loss of consciousness. Hyperthermia (>41°C), tachycardia (>160 beats per minute), tachypnea (20 breaths per minute), blood pressure (110/60 mmHg) and acute kidney failure were diagnosed. After a few hours of hospitalization, the patient died. A plastic bag with a white powder was found in his underwear. Analysis of the powder by another laboratory revealed cocaine hydrochloride; however, no cocaine or its metabolites were found in the biological material upon testing in our laboratory. Therefore, re-analysis of the powder was performed, and NEH was identified. Liquid-liquid extraction followed by liquid chromatography-triple quadrupole-mass spectrometry (LC-MS/MS) analysis were used for the determination of NEH in blood. The validation parameters were as follows: calibration range 1-250 ng/mL, accuracy 106.5-109.9%, precision 3.5-6.3%, recovery 90.1-96.9%, limit of detection 0.07 ng/mL and limit of quantification 1 ng/mL. NEH was quantified in the blood at a concentration of 145 ng/mL. Additionally, amphetamine at low concentrations and 11-nor-9-karboksy-Δ9-tetrahydrokannabinol (THC-COOH) were detected. Our study provided information on the possible lethal concentration and toxidrome that clinicians can observe for NEH-intoxicated patients and can be helpful during the preparation of toxicology analysis reports for a court of law for proper data interpretation.

Rapid and simple multi-analyte LC-MS/MS method for the determination of benzodiazepines and Z-hypnotic drugs in blood samples: Development, validation and application based on three years of toxicological analyses.

Benzodiazepines (BZDs) and Z-drugs have been particularly important treatments for sleeping and anxiety disorders for many years. However, recently, a number of new benzodiazepines (named designer benzodiazepines, DBZDs) were synthesised, but some of them have never been used in the clinic; they reached the black drug market as new psychoactive substances and are used for recreational purposes. The abuse of these substances has led to many crimes and even deaths. Therefore, it is necessary to develop new methods for their quantification for forensic and clinical toxicology. A liquid chromatography-tandem mass spectrometry-based method was developed for the simultaneous determination of 20 classical BZDS, 4 DBZDs and 3 Z-hypnotic drugs in human whole blood. As a sample preparation step, liquid-liquid extraction requiring the use of only 0.5 mL of blood sample and 1 mL of extraction solvent was applied. The selectivity, linearity, carry-over effects, limits of detection (LOD) and quantification (LOQ), precision, accuracy (both intra- and inter-day assays) and recovery were evaluated for validation. Calibration curves were linear with r values > 0.98. The LODs ranged from 0.01 to 0.33, and the LOQs were assumed to be 1 ng/mL. Inter-day precisions and accuracies were in the ranges of 87.8% - 108.5% and 1.8% - 11.2%, respectively. The recovery values ranged from 81.0% to 106.7%. The developed method proved to be sensitive, specific, simple, and fast and can be quickly modified and expanded for new compounds by the optimization of MRM. The method was applied for analysis of blood samples in 145 toxicological cases over a three-year study (2017 - 2019), which allowed us to obtain information on the prevalence of the use of these substances. The most frequently determined compounds were nordazepam (87 cases; 60%), diazepam (81 cases; 55.9%), temazepam (72 cases; 49.7%), oxazepam (56 cases; 38.7%), and midazolam (36 cases; 24.8%). The ranges of concentrations were wide and are presented as box plots. The results were used for the preparation of medico-legal opinions, which proved the utility of the method for routine toxicology analyses.

Blood concentrations of a new psychoactive substance 4-chloromethcathinone (4-CMC) determined in 15 forensic cases.

PURPOSE: The 4-chloromethcathinone (4-CMC) is a synthetic derivative of cathinone and belongs to new psychoactive substances. Neither data on the effects of 4-CMC on the human body, nor on nontoxic, toxic and lethal concentrations in biological materials have been published in the literature. This paper describes the results of an analysis of the blood concentrations of 4-CMC determined in 15 forensic cases related to nonfatal intoxication including driving under the influence, and fatalities including overdoses, suicide and traffic accidents. METHODS: A new method for the quantification of 4-CMC using gas chromatography-mass spectrometry (GC-MS) was developed. The symptoms of 4-CMC use were also studied based on an analysis of the documents prepared during the collection of samples or at autopsies. RESULTS: The limits of detection and quantification of the method for blood samples were 0.3 and 1 ng/mL, respectively. The calibration curve was linear in the studied concentration range (1-500 ng/mL) with the correlation coefficient at 0.9979. The extraction recoveries varied in the range of 94.3-98.8%. The accuracy and precision were acceptable. The determined concentrations in nonfatal cases ranged from 1.3 to 75.3 ng/mL, and in fatalities from 56.2 to 1870 ng/mL. CONCLUSIONS: Our study can assist in the recognition of the possible effects caused by 4-CMC and can be helpful during the preparation of forensic toxicological opinions for courts of law. The validation parameters indicate the sensitivity and accuracy of the method. This is the first work presenting a validated method for the determination of 4-CMC in blood samples by GC-MS.

Determination of MDPBP in postmortem blood samples by gas chromatography coupled with mass spectrometry.

ABSTRACT: MDPBP (1-(3,4-methylenedioxyphenyl)-2-(1-pyrrolidinyl)-1-butanone) is a new psychoactive substance sold on the black market. It has been a controlled drug of abuse in Poland and China since 2015 as some toxic and fatal cases connected with use of synthetic cathinone derivatives were observed. The fatal case outlined here concerns a 19-year-old man, who was found dead with an envelope containing white powder lying nearby the cadaver. The analyses of the powder revealed a presence of MDPBP. Due to this, blood was tested for routine toxicological analysis for traditional drugs and for MDPBP by liquid-liquid extraction procedure with 1-chlorobutane followed by GC-MS analysis. Full validation of proposed method was performed. Limit of detection and limit of quantification were 10.1 and 30.4 ng/cm3, respectively. Calibration curve was linear in studied concentration range (25-1000 ng/cm3) with a correlation coefficient 0.9946. The trueness and inter-day precision expressed as recoveries and CV values were investigated at 3 concentrations: 25, 250, and 1000 ng/cm3. The CV values were less than 20 % in the lowest concentration and less than 15 % in other concentrations what met the internationally established acceptance criteria for bioanalytical methods. It indicates good precision and accuracy of the method. The analysis of blood sample showed very high concentration of MDPBP (9.32 µg/cm3), which suggests possibility of overdosing. To the best of our knowledge, this is the first work which presents determination of MDPBP in blood by GC-EI-MS method and the third fatal accident report of MDPBP abuse.