Forensic Toxicology最新文献

Purpose: Methyl (S)-2-(1-7 (5-fluoropentyl)-1H-indole-3-carboxamido)-3,3-dimethylbutanoate (5F-MDMA-PICA) intoxication in 1.5-year-old child was presented, together with diagnostic parameters discussion and 5F-MDMB-PICA determination in biological material. Furthermore, 5F-MDMB-PICA metabolites were identified in a urine sample as markers of exposure in situation when a parent compound is not present in specimens.

Methods: Drugs and metabolites were extracted from serum and urine with ethyl acetate both under alkaline (pH 9) and acidic (pH 3) conditions. Hair, after decontamination and pulverization, were incubated with methanol (16 h, 60 °C). The analysis was carried out using ultra-high-performance liquid chromatography-tandem mass spectrometry. For the identification of 5F-MDMB-PICA metabolites, an urine sample was precipitated with cold acetonitrile. Analysis was performed using ultra-high-performance liquid chromatograph with quadrupole time-of-flight mass spectrometer.

Results: 5F-MDMB-PICA was determined only in serum sample at concentration of 298 ng/mL. After 1 year, when analysis was repeated, concentration of synthetic cannabinoid in the same sample was only 17.6 ng/mL which revealed high instability of 5F-MDMB-PICA in serum sample. Eight 5F-MDMB-PICA metabolites were identified in urine sample, including two potentially new ones with m/z 391.18964 and m/z 275.14016.

Conclusions: Toxicological analysis confirmed a 1.5-year-old boy intoxication with 5F-MDMB-PICA. Besides the parent drug, metabolites of 5F-MDMB-PICA were identified, including two potentially new ones, together with possible metabolic reactions which they resulted from. Metabolites determination could serve as a marker of 5F-MDMB-PICA exposure when no parent drug is present in biological material.

Purpose: The present review aims to provide an overview of methods for the quantification of 2,5-dimethoxy-amphetamines and -phenethylamines in different biological matrices, both traditional and alternative ones.

Methods: A complete literature search was carried out with PubMed, Scopus and the World Wide Web using relevant keywords, e.g., designer drugs, amphetamines, phenethylamines, and biological matrices.

Results: Synthetic phenethylamines represent one of the largest classes of "designer drugs", obtained through chemical structure modifications of psychoactive substances to increase their pharmacological activities. This practice is also favored by the fact that every new synthetic compound is not considered illegal by existing legislation. Generally, in a toxicological laboratory, the first monitoring of drugs of abuse is made by rapid screening tests that sometimes can occur in false positive or false negative results. To reduce evaluation errors, it is mandatory to submit the positive samples to confirmatory methods, such as gas chromatography or liquid chromatography combined to mass spectrometry, for a more specific qualitative and quantitative analysis.

Conclusions: This review highlights the great need for updated comprehensive analytical methods, particularly when analyzing biological matrices, both traditional and alternative ones, for the search of newly emerging designer drugs.

Purpose: Decarboxylation of Δ⁹-tetrahydrocannabinolic acid (Δ⁹-THCA) to Δ⁹-tetrahydrocannabinol (Δ⁹-THC) by heating is a common method for determining total Δ⁹-THC. In the manual for cannabis identification and analysis, the United Nations Office on Drugs and Crime (UNODC) proposed decarboxylation conditions. Although the manual's primary analytical target is Δ⁹-THC, some reports also quantified cannabidiol (CBD). The authors assessed the efficiency of decarboxylation of Δ⁹-THCA and cannabidiolic acid (CBDA), a carboxylated form of CBD, under four decarboxylation conditions, including the UNODC condition.

Methods: Δ⁹-THCA and CBDA were heated in 2-mL glass vials at 150 °C for 12 min after the following treatment: condition A involves the addition of ethanol without capping, condition B involves non addition of solvent without capping, condition C involves non addition of solvent with capping, and condition D (UNODC condition) involves the addition of 0.5 mg/mL tribenzylamine (TBA) in ethanol without capping. The residue after heating was dissolved in methanol and then analyzed by high-performance liquid chromatography.

Results: The production of Δ⁹-THC and CBD was low (≤ 10.1%) under conditions A and B. Under condition C, Δ⁹-THC production was increased (53.4%), but CBD production was hardly improved (11.7%). Under condition D, Δ⁹-THC and CBD production dramatically increased to 83.2 and 71.0%, respectively.

Conclusions: These findings indicated that TBA improved the production of Δ⁹-THC and CBD from their carboxylated forms; however, even in the presence of TBA, their production did not reach 100%. Forensic toxicologists should understand the effectiveness and limitations of decarboxylation under the UNODC condition.

Purpose: Methyl-2-(1-(4-fluorobutyl)-1H-indazole-3-carboxamido)-3,3-dimethylbutanoate (4F-MDMB-BINACA) is a newly emerging synthetic cannabinoid receptor agonists (SCRA) first described in 2018 in both Europe and the United States. Two fatal cases are reported caused by simultaneous consumption of 4F-MDMB-BINACA and ethanol.

Methods: The victims were brothers who were both found deceased after consuming 4F-MDMB-BINACA and ethanol. Post-mortem toxicological analyses of blood and urine were carried out by supercritical fluid chromatography tandem mass spectrometry (SFC-MS/MS) and headspace gas chromatography with flame ionization detection (HS-GC-FID).

Results: The concentration of 4F-MDMB-BINACA in the postmortem blood was 2.50 and 2.34 ng/mL, and blood alcohol concentration was 2.11 and 2.49 g/L, respectively.

Conclusion: According to the reported cases and reviews of the scientific literature, concurrent ethanol consumption should amplify the toxicity of SCRAs. The threshold SCRA concentration for fatal overdose can be estimated ng/mL level (0.37-4.1 ng/mL according to the reported cases) in cases in which 1.5-2.5 g/L of ethanol is present in the blood.

Purpose: In the present study, a method for the detection of 25 psychoactive substances in cerumen was developed and validated. This method targets opiates, cocaine, antidepressants, benzodiazepines, antipsychotics and antiparkinsons.

Methods: Analysis was performed on a SCIEX Triple Quad 6500+ system after liquid-liquid extraction. Methanol with 1% acetic acid was chosen as the extraction solvent. After the addition of the solvent, samples were vortexed, sonicated, centrifuged and directly injected into the liquid chromatography-tandem mass spectrometry system.

Results: The method was found to be selective and sensitive (limit of detection: 0.017 ng-0.33 ng/mg), the assay was linear for all analytes with linear regression coefficient ranging 0.9911-1.00. The values for intra-assay precision was between 4.34 and 14.6% and inter-assay precision between 5.81 and 17.7%, with accuracy within the acceptable criteria for all analytes. All analytes in cerumen specimens were stable for 48 h at 4 °C and 72 h at - 20 °C, whilst no significant matrix effect or carryover was observed. Applicability was proven by analyzing cerumen samples from 25 deceased with a history of drug abuse. All analytes were detected in real samples, thus confirming the sensitivity of the developed method.

Conclusions: According to our knowledge, it is the first time that a method for the simultaneous detection of 25 psychoactive drugs in cerumen was developed, fully validated and finally applied to 25 postmortem samples.

Purpose: Diphenhydramine is an antihistamine drug widely used to alleviate symptoms caused by allergies and the common cold. Diphenhydramine-involved fatalities have been reported in the past but usually involving overdose by ingestion. We report a peculiar case of fatal hypothermia during non-winter season involving topical diphenhydramine.

Methods: A 23-year-old male with no known preexisting medical conditions was found dead in the bathroom of his apartment with a small amount of running water on his back. Postmortem examinations and toxicological analysis on blood and urine were performed.

Results: Color difference was apparent between the right and left cardiac blood. Wischnewski spots were observed in the gastric mucosa. Histological examination revealed no obvious findings that could attribute to serious cardiovascular events. Drug screening by gas chromatograph-tandem mass spectrometry (GC/MS/MS) detected diphenhydramine in blood and urine. Further quantification revealed the postmortem concentrations to be 0.44 μg/mL in blood and 2500 μg/mL in urine.

Conclusions: The cause of death was determined to be hypothermia. Diphenhydramine-induced drowsiness and possible intrinsic cardiac factor may have led to prolonged impaired consciousness, preventing his ability to escape from the running cold water leading to hypothermia and death.

Purpose: The information on analytical methods for 4-quinazolinone recreational drugs, such as methaqualone, etaqualone and 2-methoxyqualone, is almost scant. In this study, product ion spectra of gas chromatography-tandem mass spectrometry (GC-MS/MS) with different collision energies were presented for these drugs. Because 2-methoxyqualone is a new recreational drug discovered in dubious tablets very recently, much more detailed data obtained by different types of mass spectrometry instruments, and quantification data of 2-methoxyqualone in the tablet together with its validation were demonstrated.

Methods: The methods for analyses were GC-MS/MS, high-resolution ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry and liquid chromatography-tandem mass spectrometry.

Results: The GC-MS/MS product ion spectra of the three compounds with different collision energies have not been reported before. They were very useful to tentatively identify unknown compounds. If a reference standard is available, the final identification and quantification can be achieved by measurements of product ion spectra and in selected reaction monitoring mode very easily by GC-MS/MS. The final identification and quantification for the new 2-methoxyqualone were performed in this way. The content of the compound was 69.8 ± 0.5% (w/w) in the tablet. Acetaminophen and caffeine coexisted in the tablet with approximate concentrations at 10 and 5%, respectively.

Conclusions: In this article, we have presented product ion spectra of methaqualone, etaqualone and 2-methoxyqualone at different collision energies by GC-MS/MS for the first time. In addition, this is the first paper to describe the details of quantification of 2-methoxyqualone in the authentic seized product.

Purpose: This study aims to develop and validate a rapid, simple, and efficient bioanalytical method for the simultaneous quantification of phenobarbital and barbital in human whole blood using liquid-liquid extraction combined with direct analysis in real time (DART) and high-resolution mass spectrometry (HRMS).

Method: Phenobarbital-d5 and aprobarbital were selected as internal standards (ISs) of phenobarbital and barbital, respectively. A mixed solvent of o-xylene and ethyl acetate at a ratio of 1:6 was used to extract analytes of interest and ISs from 100 μL of human whole blood samples. Phenobarbital and barbital were detected by DART-HRMS. The proposed method has been validated in accordance with United States Food and Drug Administration Guidelines for Bioanalytical Method Validation in terms of selectivity, linearity, accuracy, precision, matrix effect, recovery, stability, and dilution integrity.

Results: The lower limits of quantification (LLOQs) of phenobarbital and barbital were both 10 ng/mL. The linearities were in the range of 10-1000 ng/mL (R² ≥ 0.99). The mean recovery values of phenobarbital and barbital were 99.7% and 88.1%, respectively. The interday and intraday precision values were less than 10.4%, and the interday and intraday accuracy values ranged from 87.6 to 106.7%. Furthermore, the validated method was applied to four cases of phenobarbital poisoning at the Shanghai Institute of Forensic Science.

Conclusion: The developed and fully validated method enabled the simultaneous quantification of phenobarbital and barbital in human whole blood and was successfully applied to authentic cases.