The stability of cyanide in human biological samples. A systematic review, meta-analysis and determination of cyanide (GC-QqQ-MS/MS) in an authentic casework 7 years after fatal intoxication.

A 30 year old man was found with no signs of life in front of the house. The cyanide concentration in blood and urine was determined five years after the man's death. What is more, a stability study was conducted for 730 days in an authentic casework blood sample. Sample preparation procedure included precipitation with methanol:water mixture, solid phase extraction (SPE) and derivatization with the use of PFB-Br (pentafluorobenzyl bromide). The sample was analyzed using GC-QqQ-MS/MS (gas chromatopraphy coupled with tandem mass spectrometry) isotope dilution method. Separation was done using a SH-RXI-5MS column (30 m x 0.25 mm, 0.25 µm). Detection of PFB-CN and PFB-13CN was achieved using a triple-quadrupole mass spectrometer with an electron ionization (EI) ion source in multiple reaction monitoring (MRM) mode. After 5 years from the man's death, cyanide concentration was: 1900 ng/mL in blood and 500 ng/mL in urine. Stability study performed in an authentic blood sample 6 and 7 years after the man's death revealed cyanide concentrations of 1898.2 ng/mL and 1618.7 ng/mL, respectively. While spectrophotometric and colorimetric methods recorded both decrease and increase in cyanide concentration over time, newer chromatographic methods mainly indicate a decrease. The studies presented in this paper seem to confirm this trend. However, in order to interpretate the results of cyanide concentration in biological material reliably, more research is still necessary.

Determination of Prostaglandins (Carboprost, Cloprostenol, Dinoprost, Dinoprostone, Misoprostol, Sulprostone) by UHPLC-MS/MS in Toxicological Investigations.

Prostaglandins have stimulative influence on the human uterus and therefore were introduced to medical treatment in reproductive healthcare as labor inductors or abortifacients. The UHPLC-ESI-QqQ-MS/MS method was developed for six prostaglandins: carboprost, cloprostenol, dinoprost (PGF2α), dinoprostone (PGE2), misoprostol and sulprostone (substances for pregnancy termination) in pharmaceutical samples and was applied for the toxicological examination of pills containing misoprostol (collected during gynecological examination). There were used two internal standards: misoprostol-d5 and PGF2α-d4. The quantification of analytes was performed in the MRM mode. The linearity of method was in the range from 0.1 to 10 µg/mL, with a coefficient of determination above 0.997 (R2) for each compound. The precision and accuracy values did not exceed ±5.0%. Analysis of the pills revealed the presence of two substances: misoprostol and diclofenac. Misoprostol and diclofenac dose per sample were as follows: 608.8 ng (sample 1), 708.4 ng (sample 2), 618.8 ng (sample 3) and 67.7 mg (sample 1), 65.3 mg (sample 2) 67.3 mg (sample 3), respectively. A simple, precise and reliable method can be applied for routine examinations in terms of clinical and forensic toxicology examinations as well as in quality control of drugs for pharmaceutical purposes (original drugs and counterfeit medications).

Nitrites: An Old Poison or a Current Hazard? Epidemiology of Intoxications Covering the Last 100 Years and Evaluation of Analytical Methods.

In recent times, there has been a concerning and noteworthy rise in the global use of sodium nitrite for suicidal purposes. This is facilitated either through the employment of specialized "suicide kits" or by acquiring sodium nitrite through alternative means. Additionally, another occurrence contributing to nitrite poisoning is the recreational utilization of nitrites in the form of volatile aliphatic esters of nitrous acid, commonly referred to as "poppers". Based on current available papers and reports on the subject of nitrates, nitrites, and poppers intoxications, an epidemiological analysis and evaluation of analytical methods were performed. A total of 128 papers, documenting a collective count of 492 intoxication cases, were identified. Additionally, in order to complete the epidemiological profile of nitrite poisoning, the authors briefly examined six cases of nitrite intoxication that were under investigation in our laboratory. Furthermore, a review of nitrite poisoning cases over the past 100 years shows that the old poison is still in use and poses a substantial risk to society.

New approach for barbiturates, phenytoin, methyprylon and glutethimide determination and fragmentation (UHPLC-MS/MS).

Barbiturates which are old pharmaceutical drugs are still widely used in medical treatment of epilepsy and for general anesthesia. To date, more than 2500 different barbituric acid analogs have been synthesized, and 50 of them were introduced into medical use over the last century. Due to their highly addictive properties, pharmaceuticals containing barbiturates are under strict control in many countries. However, by considering the worldwide problem with new psychoactive substances (NPS) the introduction of new designer barbiturate analogs into the dark market might serve a serious public health problem in the near future. For this reason there is an increasing need for application methods for barbiturates monitoring in biological samples. The UHPLC-QqQ-MS/MS method for determination of 15 barbiturates, phenytoin, methyprylon and glutethimide was developed and fully validated. The biological sample volume was reduced to only 50 µL. A simple LLE (pH 3 with ethyl acetate) was successfully applied. The lower LOQ was 10 ng/mL. The method enables differentiation of structural isomers: hexobarbital and cyclobarbital; as well as amobarbital and pentobarbital. Chromatographic separation was achieved with the use of the alkaline mobile phase (pH 9) and Acquity UPLC BEH C18 column. Furthermore, the novel fragmentation mechanism of barbiturates was proposed, which may have a great impact in identification of novel barbiturates analogs introduced to illegal marketplaces. The presented technique has a great potential to be applied in forensic, clinical and veterinary toxicological laboratories, as was evidenced by the positive results of international proficiency tests.

Methyl (S)-2-(1-7 (5-fluoropentyl)-1H-indole-3-carboxamido)-3,3-dimethylbutanoate (5F-MDMB-PICA) intoxication in a child with identification of two new metabolites (ultra-high-performance liquid chromatography-tandem mass spectrometry).

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.

A fatal case involving the highest ever reported 4-CMC concentration.

Synthetic cathinones comprise a large amount of substances present on the dark market, which creates an undeniably worldwide problem and still is posing a threat. A 22-year-old man was brought to the Emergency Room from a party, where he had ingested orally 20 g of mephedrone. The man exhibited a disorder of consciousness with no logical verbal contact and dilated pupils. Moreover, a metabolic acidosis was present. The patient died after an hour from an admission to the ER. Blood and vitreous humor collected during an autopsy were analyzed with the use of an ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-QqQ-MS/MS) with the use of C18 column in multiple reaction monitoring (MRM) mode. Both biological specimens were prepared using liquid-liquid extraction (LLE) with the use of ethyl acetate and 0.5 M ammonium carbonate water solution (pH 9). The limit of quantification (LOQ) of the method was 0.5 ng/ml in both matrices; precision and accuracy values did not exceed ±15%. Recovery of the method was in the range of 86.1%-102.7%. Determined concentrations of 4-CMC were 8542 and 9874 ng/ml in blood and vitreous humor, respectively. Other substances present in both biological materials were: atropine, diazepam, lidocaine, and its metabolite norlidocaine, as well as methcathinone and ethyl alcohol. The concentration presented in here described case is the highest ever reported 4-CMC concentration. Important aspect is also receiving other NPS by recreational users than intended, which lead to accidental poisoning (in presented case user assumed 4-CMC was 4-MMC).

An ultra-sensitive UHPLC-QqQ-MS/MS method for determination of 54 benzodiazepines (pharmaceutical drugs, NPS and metabolites) and z-drugs in biological samples.

Benzodiazepines exhibit central nervous system depressive activity as well as sedative, hypnotic, and anticonvulsant properties, which enable to use them as medical treatment in anxiety, epilepsy, insomnia and alcohol withdrawal syndrome. However, from 2000s illegal benzodiazepine derivatives have started to emerge on illicit drug market as new psychoactive substances (NPSs) monitored in many countries. Analysis of both pharmaceutical drugs and NPSs from benzodiazepines group could be challenging, as usually very low concentrations need to be determined. Thus, an ultra-sensitive UHPLC-QqQ-MS/MS method was developed for simultaneous determination of 54 benzodiazepines (pharmaceutical drugs, NPS and their metabolites) and 3 z-drugs with one metabolite in biological fluid samples. The lower limit of quantification for most substances was 50 pg/mL, whereas for 17 substances as low as 10 pg/mL was achieved. Together with reduced sample volume to 100 µL it makes the developed method suitable for a sensitive multidrug toxicological analysis. Presented method was applied in routine toxicological practice as well as for the determination of benzodiazepines, z-drugs and their metabolites in 25 authentic biological fluids (blood, urine, vitreous humor and bile), both antemortem and postmortem. 19 different compounds, including benzodiazepines, their metabolites and z-drugs were determined. Antemortem blood concentrations were within 0.2-114.5 ng/mL, whereas concentrations in antemortem urine samples were 0.03-102.6 ng/mL. In postmortem specimens, concentrations ranged within 0.2-473.2 ng/mL, 0.5-94.1 ng/mL, 1.3-208.8 ng/mL and 41.5-42.0 ng/mL in blood, vitreous humor, urine and bile, respectively. The developed method is suitable for a forensic toxicology analysis, as well as clinical toxicology which is evidenced by the positive results of international proficiency tests.

A Case of Amphetamine and Methamphetamine Intoxication in Cat.

Stimulants belonging to the amphetamine group nowadays pose an undeniable worldwide threat to the life and health of users. Intoxications of domestic animals also occur, which can either be accidental or related to intentional human action. This study presents the first ever reported case of a simultaneous amphetamine and methamphetamine intoxication of a cat, along with the results of toxicological studies. Blood, urine, vitreous humor and liver were collected during the cat's autopsy and analyzed by UHPLC─QqQ─MS/MS. The sample preparation technique was based on one-step precipitation of proteins with cold acetonitrile. The determined amphetamine concentrations in the collected biological materials were 93.4 ng/mL in blood, 496.6 ng/mL in urine, 589.2 ng/mL in the vitreous humor and 291.2 ng/g in liver, respectively. Methamphetamine concentrations were 45.5 ng/mL in blood, 263.1 ng/mL in urine, 351.2 ng/mL in vitreous humor, and 97.7 ng/g in liver. Other substances were also found in the biological material, i.e., diazepam, oxazepam and nordiazepam. Cases of intentional or accidental poisoning of pets with psychoactive substances are a serious problem, carrying the risk to the health and life of the animal. Therefore, it is important to increase awareness of the high risk of poisoning of domestic animals, as well as to learn about the incompletely understood mechanisms of pharmacokinetics of various drugs in animals, including cats.

Determination of Mifepristone (RU-486) and Its Metabolites in Maternal Blood Sample after Pharmacological Abortion.

The aim of the study was the development and validation of the UHPLC-QqQ-MS/MS method for the determination of mifepristone in human blood as well as the identification and quantification of its metabolites after self-induced pharmacological abortion. The metabolic pathway in humans was proposed after examination of an authentic casework. The fast and simple preanalytical procedure was successfully applied (pH9, tert-butyl-methyl ether). The validation parameters of the method were as follows: limit of quantification: 0.5 ng/mL; coefficients of determination: >0.999 (R2), intra- and inter-day accuracy and precision values did not exceed ± 13.2%. The recovery and matrix effect were in the range of 96.3−114.7% and from −3.0 to 14.7%, respectively. Toxicological analysis of the mother's blood (collected the day after the pregnancy termination) revealed the presence of five compounds: mifepristone (557.4 ng/mL), N-desmethyl-mifepristone (638.7 ng/mL), 22-OH-mifepristone (176.9 ng/mL), N,N-didesmethyl-mifepristone (144.5 ng/mL) and N-desmethyl-hydroxy-mifepristone (qualitatively). To our knowledge, the study presented in this paper is the first report on the concentrations of mifepristone and its metabolites in maternal blood samples after performing a self-induced abortion. The established UHPLC-QqQ-MS/MS method is suitable for forensic toxicological analysis as well as in terms of clinical toxicology in future investigations (examination of pharmacokinetics, bioavailability and metabolism of RU-486).

Forensic Toxicological Aspects of Misoprostol Use in Pharmacological Abortions.

The aim of this study was establishment of an UHPLC-QqQ-MS/MS method for the deter-mination of misoprostol acid in biological specimens in cases of pharmacological abortions. Forensic toxicological examination was performed in three different biological samples (whole blood, placenta and fetal liver). The validation parameters of the method were as follows: limit of detection: 25 pg/mL; limit of quantification: 50 pg/mL, coefficient of determination: >0.999 (R2), intra- and interday accuracy and precision: not greater than 13.7%. The recovery and matrix effect were in the range of 88.3−95.1% and from −11.7 to −4.9%, respectively. Toxicological analysis of the mother's blood (collected two days after pregnancy termination) did not reveal any abortifacients; however, misoprostol acid was found in the placenta (793 pg/g) and fetal liver (309 pg/g). The second case involved a fetus found near a garbage container. The concentration of misoprostol acid in the placenta was 2332 pg/g. In the presented study, an extensive literature review of misoprostol pharmacokinetics studies was performed. To our knowledge, the UHPLC-QqQ-MS/MS technique presented in this paper is the first quantitative method applied for forensic toxicological purposes. In addition, postmortem concentrations of misoprostol acid in miscarried fetuses due to illegal abortions were reported for the first time.

Toxicological Aspects of Methotrexate Intoxication: Concentrations in Postmortem Biological Samples and Autopsy Findings.

The aim of this study was the establishment of a UHPLC-QqQ-MS/MS method to determine methotrexate in postmortem biological samples and quantify the postmortem distribution of methotrexate in a case of fatal intoxication of this drug. A volume of 100 µL or 100 mg of postmortem specimens was precipitated with 400 µL of cold methanol and then analyzed using UHPLC-QqQ-MS/MS. The validation parameters of the method were as follows: limit of quantification: 0.1−1.0 ng/mL or ng/g, coefficient of determination: >0.998 (R2), matrix effect, intra- and inter-day accuracies and precisions: not greater than 13.6%, 14.8% and 17.4%, respectively. The recoveries were: 89.0−113.6%. The postmortem distribution studies revealed methotrexate concentrations as follows: blood­7.2 ng/mL, vitreous humor­0.8 ng/mL, liver­43.7 ng/g, kidney­20.6 ng/g, bone marrow­29.9 ng/g, lumbar vertebra­20.0 ng/g. The highest concentrations of methotrexate after poisoning were found in the tissues with the most rapidly dividing cells. The method described is simple, precise and selective. Methotrexate concentrations can be routinely determined in postmortem specimens. Determination of methotrexate in the postmortem biological material is possible after a few days of intensive treatment.

Diclofenac Concentrations in Post-Mortem Specimens-Distribution, Case Reports, and Validated Method (UHPLC-QqQ-MS/MS) for Its Determination.

The aim of the research was to establish a sensitive method for the quantification of diclofenac in postmortem samples. The developed method was applied in six cases: three fetuses in which the use of abortion pills by their mothers was suspected, one case of duodenal ulcer perforation, one case of traffic accident with fatal outcome, and one acute renal failure in which the distribution of diclofenac was examined. The analyses were performed using liquid-liquid extraction of postmortem samples and the quantification of diclofenac via ultra-high performance liquid chromatography, coupled with triple quadrupole tandem mass spectrometry. Gradient elution using a C18 column was applied. Electrospray ionization measurement in positive multiple reaction monitoring mode was used. Diclofenac-d4 was used as an internal standard. The validation parameters were as follows: lower limit of quantification: 0.5 ng/mL, linearity of calibration curve: 0.5-500 ng/mL, intra- and interday accuracies and precisions: not greater than 15%; recovery values: 72.0-102.2%, and matrix effect: 2.2-28.0%. The developed method enabled the determination of diclofenac in human postmortem biological fluids (blood, urine, vitreous humor, bile, and stomach content), tissues (placenta, kidney, liver, and heart), and in exhumated fetus bones, with high recovery, sensitivity, precision, and accuracy.

The dark side of social media: Two deaths related with chloroform intoxication.

A suicide pact is an agreement between people to commit suicide together, which usually takes place at the same time, in the same place, by using the same method. Social media serve as a way of communication between people. Thus, they use such platforms to find potential suicide pact partners. Chloroform, although being regarded to as a slightly forgotten poison, is still linked to homicide and suicide cases. Death due to an acute chloroform ingestion may be a result of central nervous system depression. In this paper, we present application of headspace gas chromatographic method using a dual column/dual flame ionization detector (HS-GC-FID/FID) for the determination of chloroform in two fatal intoxication cases, as well as chloroform stability study. Analysis of biological samples revealed chloroform concentrations of 135.8, 16.1, 8.1, and 37.1 µg/ml in blood, urine, vitreous humor, and bile, respectively. Kidney, liver, and muscle specimens contained 119.5, 99.6, and 28.4 µg/g of chloroform, respectively. The results of stability studies indicate the highest decrease of chloroform in room temperature, so it is advised to store samples in a freezer. The addition of sodium fluoride is recommended as in blood samples collected to the test tubes without any preservative agent, the detection of chloroform after 91 days is almost impossible. It is important to emphasize that even old poisons can cause a lot of concerns today, as here described cases are linked to chloroform intoxication, as well as with possible danger which social media bring about nowadays.

Simultaneous poisoning of 48 birds of prey - bendiocarb determination with the use of UHPLC-ESI-MS/MS method in fatal case from Eastern Europe.

Aim: Bendiocarb is used against a wide range of insects but has already been withdrawn from the market in some countries. It poses a high risk to birds as they can accidentally ingest it while searching for food, followed by toxic effects. This paper presents the results of toxicological and histopathological studies of 48 cases of intentional birds of prey poisoning with bendiocarb in Eastern Europe, specifically Poland. Material and methods: A novel ultra-high-performance liquid chromatography-triple quadrupole-tandem mass spectrometry (UHPLC-ESI-MS/MS) method for bendiocarb determination in animal liver samples was developed and fully validated. The sample preparation technique was based on one-step precipitation of proteins with cold acetonitrile. The internal standard used was carbaryl-d7. Full time of analysis was less than 10 minutes. The application of the UHPLC-ESI-MS/MS method allowed us to achieve the lowest LOQ (1 ng/g) of bendiocarb in biological samples to date. Results: Necropsies and histopathological examinations of common ravens (Corvus corax), western marsh harriers (Circus aeruginosus), red kites (Milvus milvus), and a white-tailed eagle (Haliaeetus albicilla) revealed multi-organ toxicity manifested as congestion, oedema, or stagnation of blood. An analytical investigation confirmed the presence of bendiocarb in liver in the 1808-7721 ng/g range. Furthermore, the presence of this compound was qualitatively confirmed in the stomach and beak contents and also in the bait located near the deceased animals. Conclusions: A comprehensive forensic examination is crucial to monitor wildlife fatalities, especially applying a combined analytical and histopathological approach to identify and eliminate highly toxic substances which pose a threat to the ecosystem.

Severe poisoning after smoking a mixture of 4-fluoroisobutyryl fentanyl (4-FiBF) and alpha-pyrolidinoisohexaphenone (α-PiHP).

CONTEXT: Intoxications after ingestion of new psychoactive substances are currently one of the most challenging issues in clinical toxicology. Synthetic cathinones represented the largest group of drugs seized in 2020, but the increasing distribution of fentanyl analogues is resulting in a growing global opioid crisis. In addition, synthetic opioids may be intentionally combined with psychostimulants by drug manufacturers to reduce depressive effects. We report a case of severe poisoning after smoking a mixture of 4-fluoroisobutyryl fentanyl (4-FiBF) and alpha-pyrrolidinoisohexaphenone (α-PiHP). CASE DETAILS: A 29-year-old male was found out of conscious in his apartment and taken to the Intensive Care Unit. Examinations revealed pinpoint pupils, slight respiratory acidosis, leukocytosis as well as body temperature of 39.4 °C and increased creatinine with decreased eGFR level. Toxicological analysis of biological samples revealed presence of 4-FiBF and α-PiHP in concentrations: 87.7 ng/mL and 5.0 ng/mL (blood) and 2291.0 ng/mL and 722.2 ng/mL (urine), respectively. After 4 days, the patient was discharged home. DISCUSSION: Unique combination of clinical symptoms was a result of a simultaneous 4-FiBF and α-PiHP intoxication. To our knowledge, this is the first case of ingestion such unusual mixture of new psychoactive substances with a full description of medical treatment.

A novel procedure for stabilization of azide in biological samples and method for its determination (HS-GC-FID/FID).

Sodium azide is an old poison with toxicity comparable to potassium cyanide. It would seem to be completely forgotten however, between 2000 and 2020, the number of intentional ingestions and murders committed with sodium azide significantly increased. Furthermore, due to its extreme instability, sodium azide is difficult to detect, which poses an additional risk when used to commit a crime. In this study, the epidemiology of sodium azide exposures between 1920 and 2020 was investigated. For the determination the azide concentration in biological samples, a simple, precise and selective headspace gas chromatography method (HS-GC-FID/FID) was developed and fully validated. The limit of quantification was 0.65 µg/mL; and the limit of detection was 0.35 µg/mL; precision and accuracy did not exceed 20%. The stability study was conducted for various biological fluids (urine, bile, blood, gastric content) for 91 days in the refrigerator (4 °C) and the method for stabilization of azide was presented. The addition of a mixture of borax and sodium fluoride (w/w 3:1) to the test tubes can stabilize this poison. The described unique technique of collecting the biological samples poses a great potential for azide detection in clinical and toxicology laboratories even long time after human exposure to this substance.

Application of ultra-sensitive GC-QqQ-MS/MS (MRM) method for the determination of diclofenac in whole blood samples without derivatization.

Diclofenac is one of the most frequently prescribed nonsteroidal anti-inflammatory drugs (NSAID) worldwide. Although it is considered a relatively safe drug, it exhibits high toxicity to some animal populations (e.g., raptors). An ultra-sensitive gas chromatography method, coupled with tandem mass spectrometry (GC-QqQ-MS/MS) with an electron impact (EI) ionization source for diclofenac determination in whole blood samples without a derivatization procedure, was developed and fully validated. Diclofenac-d4 was used as an internal standard. The determination of analytes was performed in the multiple-reaction monitoring (MRM) mode. The method was linear in the range from 0.1 to 200 ng/mL, with a coefficient of determination of 0.999 (R2). The lower limit of quantification was 0.1 ng/mL, and the detection limit was 0.05 ng/mL. The blood samples (200 µL) were prepared by liquid-liquid extraction (pH3) with ethyl acetate. The intra- and interday accuracies and precisions did not exceed 15%. Recovery and matrix effect values were in the range of 92.2-105.9% and -7.8 to 5.9%, respectively. The developed method was applied in authentic blood samples. A simple and precise GC-QqQ-MS/MS method can be potentially applied for routine clinical, toxicological and environmental analysis.

Old Poison, New Problem: Cyanide Fatal Intoxications Associated with Internet Shopping.

Widespread access to the Internet has an increasing influence on how suicides are committed. On websites such as eBay® or Amazon.com® highly toxic substances including cyanides are available for purchase. In the last 5 years, a few fatal intoxications associated with Internet shopping and buying "suicide kits" have been reported. Epidemiology of intoxications reported by American Association of Poison Control Centers between 2000-2018 shows that about 10% of all exposures to cyanide were related to suicide attempts and intentional ingestion of this substance. In order to determine the cyanide concentration in four fatal intoxication cases associated with Internet shopping, a headspace gas chromatography with dual column/dual flame ionization detector (HS-GC-FID/FID) method was validated and applied to casework. The method was linear in range, from 1 to 50 µg/mL, with a coefficient of determination of 0.999 (R2). The limit of quantification was 1.0 µg/mL; the detection limit was 0.5 µg/mL. Intra- and inter-day validation precision and accuracy did not exceed 10% and 15%, respectively. Recovery and matrix effect values ranged from 94.8- 103.8% and -5.2─3.8%, respectively. The cyanide concentrations were determined in biological fluids (blood, urine, bile, vitreous humor, gastric content) and postmortem tissue samples (spleen, kidney, liver, brain). The headspace gas chromatographic method, which is routinely used in clinical and forensic toxicology to quantify ethanol with its congeners (methanol, acetone, isopropanol, n-propanol and n-butanol), can be also applied to determine cyanide in intoxication cases. The global problem of a high number of suicides each year, requires increasing and more restrictive control of highly toxic substances available online as well as caution monitoring of human exposure to cyanide. This old and well known poison is being increasingly used nowadays for suicidal purposes, therefore determination of cyanide in biological samples is still important in terms of clinical and forensic toxicology.

The application of headspace gas chromatographic method for the determination of ethyl alcohol in craft beers, wines and soft drinks.

The increasing interest of consumers in the still-developing craft beer market and the strict tax-related legal regulations concerning alcoholic beverages require precise methods for quality control. Determination of ethyl alcohol concentration was performed in 167 samples of alcoholic beverages (craft beers, soft drinks, wines, and cider). We applied headspace gas chromatography using a dual column/dual flame ionization detector (HS-GC-FID/FID), a technique routinely used in forensic toxicology. The method was linear in range, from 0.01 to 20.0%, with a coefficient of determination of 0.999 (R2). The limit of quantification was 0.01%; the detection limit was 0.003%. Furthermore, very good validation parameters were achieved (precision and accuracy below 5%). The samples were analyzed for compliance with EU standards and recommendations of The Beer Judge Certification Program. Moreover, the content of trace quantities of volatile compounds and fusel alcohols (1-propanol, 2-propanol, acetone, and acetaldehyde) was found in the majority of alcoholic beverages.

A novel simple and precise method for the determination of azide impurity in sartans using headspace gas chromatography with two dissimilar capillary columns and two flame ionization detectors (HS-GC-FID/FID).

Determination of azide as an impurity in medicinal products was performed for the following sartans with tetrazole functional group (synthesized with the use of azide ion): candesartan, losartan, irbesartan, olmesartan medoxomil, and valsartan. This was achieved using headspace gas chromatography using a dual column/dual flame ionization detector (HS-GC-FID/FID). The method was linear in range, from 5.0-30.0 µg/g, with a coefficient of determination of >0.998 (R2). The limit of quantification was 5.0 µg/g and the detection limit was 1.9 µg/g. The sample preparation procedure is fast and simple. The validation procedure was performed in accordance with International Conference on Harmonization (ICH) and Pharmacopeia guidelines. Moreover, besides the content of azide ions, trace quantities of residual solvents (methanol, ethanol, acetone, isopropanol) were found in the majority of sartan tablets.