Toxicological Diagnosis Research Articles

Simultaneous determination of methanol, ethanol, and formic acid in human serum by HSGC-MS: Method development, validation, and application

The concurrent assessment of methanol, ethanol, and formic acid is imperative for accurate clinical toxicology diagnosis in cases of methanol poisoning. Here, we reported a very simple and reliable headspace gas chromatography coupled with mass spectrometry (HSGC-MS) method for simultaneous quantitative determination of methanol, ethanol and formic acid in blood samples. The derivatization variables for formic acid were optimized. The method exhibits high sensitivity, good selectivity and effective separation factor for methanol (6.51 min), ethanol (8.29 min), and formic acid (11.41 min). The method demonstrates excellent reproducibility and accuracy. The limit of detection (LOD) and the limit of quantification (LOQ) were determined to be 3.14–5.83 μg/mL and 10.47–19.34 μg/mL, respectively. Finally, this method was successfully used for measuring the levels of methanol, ethanol, and formic acid in the serum of patients involved in actual methanol poisoning incidents.

Chemical and Toxicological Diagnosis of Acute Poisoning with Doxylamine, Zaleplon, and Phenazepam

BACKGROUND The market of hypnotic and sedative drugs is being updated due to the high toxicity of barbiturates and the limitations of their use. Currently, safer drugs such as Z-drugs, Doxylamine, and some benzodiazepine derivatives are often prescribed for the treatment of anxiety and insomnia, but they can cause acute poisoning if overdosed or in case of nonmedical use.AIM To establish an affordable express thin-layer chromatography (TLC) technique for preliminary screening detection of Doxylamine, Phenazepam and Zaleplon in order to diagnose acute poisoning.MATERIAL AND METHODS Thin-layer chromatography (TLC) and gas chromatography with mass selective detection (GC-MS) methods were used. Urine samples from patients with symptoms of acute Doxylamine, Zaleplon, Phenazepam poisoning, and model urine samples were prepared by liquid-liquid extraction at pH 9.0 with chloroform for TLC analysis, with ethyl acetate-diethyl ether mixture (1:1) for GC-MS.RESULTS We developed the TLC method of Doxylamine, Zaleplon and Phenazepam detection which helps reveal their presence in the patient’s urine, as well as distinguish one from another in case of similar toxic symptoms. The GC-MS method was used for confirmatory analysis. Compared to confirmatory methods, the developed technique of TLC screening is expressive, does not require expensive high-tech equipment, while allowing to differentiate Doxylamine, Zaleplon and Phenazepam from each other and from other toxicologically significant psychoactive substances detected in general screening.

Toxic Agents in Ruminants Diagnosed in the Pathological Anatomy Service of the UFRRJ, Rio de Janeiro - Brazil

Background: Toxic agents are chemical substances or physical agents that, when interacting with living organisms, cause harmful effects. For animals, toxic products include those intended to combat endo and ectoparasites, rodenticide products, and heavy metals. Minerals and dietary additives, even if essential to the animal, can become toxic agents, among which sodium chloride, copper, urea, and ionophore antibiotics stand out. This study aimed to survey the diagnoses of accidental poisoning in ruminants over 65 years as recorded in the files of the Pathological Anatomy Sector of the Federal Rural University of Rio de Janeiro.Materials, Methods & Results: The diagnoses of poisoning by ticks, rodenticides, heavy metals, macro and micronutrients, and dietary additives in ruminants were made based on the association of epidemiological, clinical, and anatomopathological findings and, in some cases, by histochemical (rubeanic acid and Masson trichrome) and toxicological examinations. A review of data recorded over 65 years identified 372 poisonings in ruminants. Of these, 85.5% (318/372) were in bovine species and 14.5% (54/372) in goats, sheep, and buffaloes. The outbreak of poisoning by organophosphates resulted in the death of 16 cattle that ingested contaminated broken rice and corn. The spraying of this product on the bags was intended to control insects. Intoxication due to excessive administration of abamectin resulted in the intoxication of 16 calves, in two distinct farms. Toxicosis caused by coumarin derivatives resulted in the death of six cattle after accidental ingestion of these rodenticides near the pens. Arsenic poisoning occurred due to ingestion of ant poison, available in bone meal and a mineral salt, through baths with arsenic-based ticks, or in cases later confirmed by toxicological analysis, resulting in the death of 109 cattle. Sodium chloride toxicosis resulted in the death of 10 sheep that became ill in two farms after excessive consumption of salt and private access to water. The diagnosed copper poisoning resulted in the death of 165 ruminants (154 cattle, 10 sheep, and 1 goat). Urea poisoning occurred due to excessive ingestion by 13 cattle and 4 buffaloes, without prior adaptation. Cases of poisoning by ionophore antibiotics occurred in 11 sheep, 18 buffaloes, and 4 cattle. In all cases, the source of exposure was mineral salt and/or feed with an excess of ionophores. The results of the laboratory tests varied according to the type of intoxication.Discussion: Among the means of diagnosing poisoning by toxic agents, minerals, and dietary additives, anamnesis should be detailed and highlighted to present all relevant information. It is the basis for toxicological diagnosis, because it generates information that helps in the definitive elucidation of cases and establishing control and prophylaxis plans, facilitates the prediction of prognosis, and directs the application of appropriate therapy, when possible. In the intoxication diagnoses reported here, the toxicological examination was important in elucidating the toxicosis caused by organophosphates, coumarin derivatives, arsenic, and copper, but the referral for toxicological analysis was previously indicated by a hypothesis generated during the anamnesis. Therefore, anamnesis becomes important yet elusive as toxicological examination leading to diagnosing intoxication.Keywords: toxicology, diagnosis, chemical substance, farm animals.Descritores: toxicologia, diagnóstico, substância química, animais de fazenda.

Toxicological Diagnosis of Severe Neutropenia Due to Levamisole

Introduction: Levamisole toxic syndrome may include several effects, such as bone marrow suppression, severe agranulocytosis, neurological symptoms, or cutaneous vasculitis. Methodology: This report emphasizes the importance of differential diagnosis in young patients with severe neutropenia by hair toxicological analyses. These analyses can reveal the presence of cocaine and his metabolites but also sometime levamisole, a synthetic drug, originally approved by the US Food and Drug Administration as an anthelmintic agent that is still encountered as one of the main contaminants of cocaine. Many physicians are not aware of this contaminant and do not take it into account when diagnosing cases of sudden severe neutropenia. Results: In cases of sudden otherwise unexplained neutropenia, the detection of levamisole in hair may represent the most efficient method for demonstrating the toxic effect of chronic levamisole exposure, because urine conventional drug testing often fails to identify the compound due to its rapid elimination (2-3 days).

Antidotes for childhood toxidromes.

BackgroundPoisoning causes significant morbidity and sometimes mortality in children worldwide. The clinical skill of toxidrome recognition followed by the timely administration of an antidote specific for the poison is essential for the management of children with suspected poisoning. This is a narrative review on antidotes for toxidromes in paediatric practice.MethodsA literature search was conducted on PubMed with the keywords “antidote”, “poisoning”, “intoxication”, “children” and “pediatric”. The search was customized by applying the appropriate filters (species: humans; age: birth to 18 years) to obtain the most relevant articles for this review article.ResultsToxidrome recognition may offer a rapid guide to possible toxicology diagnosis such that the specific antidote can be administered in a timely manner. This article summarizes toxidromes and their respective antidotes in paediatric poisoning, with an emphasis on the symptomatology and source of exposure. The antidote and specific management for each toxidrome are discussed. Antidotes are only available for a limited number of poisons responsible for intoxication. Antidotes for common poisonings include N-acetyl cysteine for paracetamol and sodium thiosulphate for poisoning by cyanide.ConclusionPoisoning is a common cause of paediatric injury. Physicians should be familiar with the recognition of common toxidromes and promptly use specific antidotes for the management of childhood toxidromes.

Laboratory toxicological diagnosis of fluoxetine poisonings

The results of laboratory diagnosis obtained during the toxicological study of human biological fluids for the presence of drugs are of key importance for determining the cause of the antidepressant poisoning.Aim. To develop the bioanalytical method for determining the antidepressant fluoxetine in the blood and urine based on the high-performance liquid chromatography with a multiwave UV spectrophotometric detection, which is suitable for laboratory toxicological diagnosis of the antidepressant poisoning. Materials and methods. The model blood and urine samples spiked with the antidepressant studied were analyzed. The extraction of the drug from biological fluids was performed with chloroform from the alkaline medium at pH of 8-9 in the presence of ammonium sulfate as a salting-out agent. The formed elements of blood were precipitated with 10 % trichloroacetic acid. The biological admixtures were removed by extraction with diethyl ether from the acidic medium and the TLC method. The chromatographic analysis was performed on a microcolumn chromatograph with a multiwave UV spectrophotometric detector on a reversed-phase C18 column.Results. The retention time of fluoxetine in extracts from the blood and urine was 23.35 ± 0.03 min. The quantitative determination was performed at λmax 260 nm by the calibration curve of the dependence of the concentration on the peak area (μg/ml) y = (9.2∙10-5 ± 1∙10-6)x. Using the sample preparation method developed 58±4 % of fluoxetine was isolated from the blood, (72 ± 4) % of the drug from the urine. Conclusions. The methods developed for the determination of fluoxetine in the blood and urine by the reversed-phase HPLC with a multiwave UVD after the liquid-liquid extraction at the stage of sample preparation have allowed to identify and determine the expected toxic and lethal concentrations of this antidepressant in biological fluids, and therefore, are suitable for the purpose of clinical and forensic toxicology.

An Overview of the Pediatric Toxidromes and Poisoning Management.

Poisoning is one of the leading causes of childhood morbidity and mortality worldwide. Despite the advancement of poison detection by modern investigation methods, the clinical skill of toxidrome recognition by combining the findings from a detailed history, thorough physical examination, and the results of basic investigations is still indispensable for the management of children with suspected poisoning. The aim was to review pediatric toxidromes and poisoning management. A literature search was conducted on PubMed (between February 1 and 15, 2020) with keywords "toxidrome" "poisoning" "intoxication" "children" and "pediatric". The search was customized by applying the appropriate filters so as to get the most relevant articles to meet the objective of this review article. Toxidrome recognition may offer a quick guide to possible toxicology diagnosis so that specific antidote can be administered in a timely manner. This article discusses a few commonly encountered toxidromes in pediatric poisoning, with an emphasis on the symptomatology and source of exposure. The antidote and specific management for each toxidrome are also discussed. Although most patients with intoxication can be managed with close observation, supportive measures and antidote treatment, it is unfortunate that antidotes are only available for a limited number of poisons responsible for intoxication. Extracorporeal toxin removal is being increasingly recognized as a mode of treatment for patients with rapid deterioration who are unresponsive to conventional management. The decision to apply such technique and the choice of modality are frequently individualized due to the paucity of high-level evidence. The various patient and toxin/medication factors involved in the decision- making process are discussed. Poisoning is a common cause of pediatric accidents and injuries. Physicians should be familiar with common toxidromes and poisoning management.

Chemical and Toxicological Diagnosis of Acute Poisoning with Clozapine, Olanzapine, Quetiapine and Risperidone

Relevance The large number of atypical antipsychotic drugs on the market , the breadth of their medical and non-medical use, and their relative affordability make atypical antipsychotics common causes of overdose, suicidal actions or non-medical use of drugs. At the same time, they remain insufficiently studied from the chemical and toxicological point of veiw.Aim od study: creation of available express method of detection of clozapine, olanzapine, quetiapine and risperidone in the urine of patients with acute poisoning.Material and methods Thin layer chromatography (TLC), gas chromatography with mass selective detection (GC-MS), and high performance liquid chromatography with mass selective detection (HPLC-MS/MS) were used. The preparation of intact urine samples with addition of standard solutions of clozapine, olanzapine, quetiapine, risperidone and urine samples of patients with symptoms of acute poisoning with given drugs was carried out by methods of liquid-liquid extraction at alkaline pH values for TLC chloroform, a mixture of ethyl acetate-diethyl ether (1:1) for GC-MS and acetonitrile for HPLC-MS/MS.Results A TLC method has been developed to detect clozapine, olanzapine, quetiapine and risperidone, which allows its the presence to be quickly revealed in the patient’s urine at the preliminary examination stage and also distinguish them from each other in case of the same type of symptoms of poisoning. For confirmatory analysis, it is advisable to use the methods of HPLC-MS/MS and GC-MS. Compared to confirmatory methods, the developed TLC-screening technique is expressive, does not require the use of expensive high-tech equipment and allows clozapine, olanzapine, quetiapine and risperidone to be differentiated from other toxicologically significant psychoactive substances found in general screening.

Fatal metaldehyde poisoning in a dog confirmed by gas chromatography

BackgroundMetaldehyde is a toxic pesticide used mainly as a molluscicide, responsible for intoxication and deaths in both humans and animals. Accidental exposure to metaldehyde in dogs is considered rare, but severe. Data concerning clinical and veterinary forensic toxicology are largely incomplete, especially regarding case reports in dogs. The present work reports a complete and detailed description of a case from the history, clinical evolution, pathological exams and toxicological diagnosis in an accidental case of metaldehyde poisoning in dog.Case presentationAn eleven-month-old, 3.0 kg, male German Spitz was presented for emergency care with acute vomiting and seizures 3 hours after suspected accidental ingestion of commercial molluscicide containing 3% metaldehyde (Lesmax®). The animal was in lateral recumbency and showed stuporous mentation, salivation, tonic-clonic status epilepticus, systemic tremors, bilateral miosis, absent palpebral, corneal, oculovestibular and gag reflexes, severely depressed spinal reflexes, dyspnea and tachycardia. Despite treatment, the patient progressed to comatose mentation and died. Necropsy examination revealed discrete lesions in the liver and central nervous system, while stomach examination revealed content of feed, activated charcoal and blue-green granules, compatible to the commercial formula of metaldehyde. Histology examination revealed extensive hemorrhage and severe centrolobular necrosis of the liver and tumefaction of Kupfer cells. Brain samples showed discrete hemorrhage and hyperemia. In order to confirm the diagnosis, samples from feces, stomach content, spleen, liver, heart, kidneys and brain were submitted gas chromatography analysis. Results confirmed the presence of metaldehyde in all samples. We describe clinicopathological abnormalities of a fatal case of metaldehyde poisoning in a dog, as well as postmortem diagnosis using gas chromatography.ConclusionMetaldehyde poisoning is rarely reported, since the diagnosis is often difficult and the notifications scarce. To our knowledge, this is the first report describing clinical signs, pathological findings and chromatographic diagnosis. This report aims to contribute to the understanding of the pathogenesis of metaldehyde intoxication, to further explore veterinary forensic toxicology diagnosis.

Toxicological Analysis Unveiling the Low Rate of Self-Reporting of Addictive/Recreative Substances in Acute Severe Drug Overdose Cases.

ObjectiveToxicological analysis (TA) is advised when assessing the prognosis and the treatment of drug overdose patients. Apart from this use, the value of TA has remained unclear. This study aimed at defining the value of TA regarding the toxicological diagnosis in severe overdose cases that involved addictive or recreational drugs (ARDs) that were used either alone or in combination with medicinal drugs.MethodsThe patients who were enrolled in the study had been admitted to our intensive care unit for the treatment of poisoning. TA was performed using advanced technologies such as mass spectrometry of blood/urine on admission. An occurrence indicated the supposed ingestion of a defined substance. Patients were included in a group depending on the combination of the occurrences of supposed ingested drugs (SID) and the results of the 1) TA: SID+, TA+; 2) SID+, not searched by TA; 3) SID−, TA+.ResultsThere were 224 occurrences of 90 substances in 70 patients. ARDs were present in 30 patients (43%). ARD accounted for 24 occurrences in the SID+, TA+ group, 10 occurrences in the SID+, not searched group and 196 occurrences in the SID−, TA+ group. In the SID+, TA+ group, 9 occurrences (69%) of ethanol were confirmed by TA. Ingestion of ethanol was invalidated in 4 occurrences (31%). In the patients who denied ethanol ingestion, TA confirmed the non-ingestion of ethanol using 30 blood measures (81%). Ethanol was involved in 57% of the patients, being the lone substance in only 1 case.ConclusionIn drug overdose instances that result in organ failure(s) and involve ARDs, self-reporting is of limited value in assessing the patients’ exposure to ARD. Multiple consumptions expose patients to unexpected drug interactions.

Toxicological diagnosis by echocardiography.

Toxicological diagnosis by echocardiography.

The impact of the introduction of a toxicology service on the intensive care unit

Objective: To examine the impact of a clinical toxicology service on toxicology patients admitted to an intensive care departmentMethods: The authors performed a retrospective chart audit of all patients presenting to Cairns Emergency Department (ED) over a five-year period from 2011 to 2016 with a toxicology diagnosis requiring Intensive Care Unit (ICU) admission. They were divided into two groups: pre-toxicology (1 April 2011 to 30 September 2012), and post-toxicology service (1 October 2012 to 31 of March 2016) introduction. Patients were identified using ED and ICU databases. Patient charts were manually searched, and data entered on a preformatted data extraction tool. The data were statistically compared pre- versus post-toxicology service introduction using univariate (t-tests and Pearson’s Chi Square) and multivariate modelling. Where appropriate, continuous variables were log transformed to enable parametric analyses.Results: There were 37 patients in the pre-toxicology and 102 in the post-toxicology group, with an increased median APACHE III J score in the post toxicology group (39 vs. 49). The introduction of a toxicology service was associated with statistically significant reductions in median ICU length of stay (LOS) (32.9 vs. 20.6 h), median duration of mechanical ventilation (29.1 vs. 20.6 h) and median time to psychiatry review (19.4 vs. 6.7 h). The reduction in ICU LOS remained statistically significant (p = 0.036) when adjusted by sex, age and duration of mechanical ventilation. There was neither increase in mortality, nor readmissions from EDSSU to ICU.Conclusions: This study has demonstrated that the introduction of a toxicology service was associated with a reduction in median ICU LOS, duration of mechanical ventilation and time to psychiatric review in patients with a toxicology diagnosis admitted to our ICU.

Chemical and Toxicological Diagnosis of Acute Poisonings with Phenazepam

Background. The relative availability of Phenazepam makes it a frequent cause of overdose, suicide and non-medical use. At the same time, it remains insufficiently studied in chemical and toxicological terms.The aim of study. to create an accessible, rapid method for detecting Phenazepam in biological matrices of patients with acute poisoning.Materials and methods. We used thin-layer chromatography (TLC), gas chromatography with a mass selective detector (GC-MS), high performance liquid chromatography with a tandem mass-selective detector (LC-MS/MS) and immunochromatographic analysis (ICA). The preparation of samples of intact urine with the addition of standard solutions of Phenazepam and real urine samples of patients with acute poisoning with Phenazepam was carried out using liquid-liquid extraction or precipitation of related components of the sample with acetonitrile. Hydrolysis and derivatization were also added in GC-MS analysis.Results. The analysis of statistics of the Department of Acute Poisonings of the N.V. Sklifosovsky Research Institute for Emergency Medicine in 2014-2016 showed that Phenazepam poisonings averaged 9.2% of the total number of admissions and mainly occurred as suicidal attempts. A technique has been developed for the detection of Phenazepam by TLC, which gives more objective results than ICA. For confirmatory analysis, it is advisable to use LC-MS/MS method for the native substance and GC-MS for the products of hydrolysis after derivatization. Compared to confirmatory methods, the developed TLC-screening technique is expressive, does not require the use of expensive high-tech equipment, difficult sample preparation, and makes it possible to reliably detect toxic and lethal concentrations of Phenazepam.

Determination of periplocymarin in human blood and urine by high-performance liquid chromatography-mass spectrometry

A simple, rapid and sensitive liquid chromatography with tandem mass spectrometry method for the determination of periplocymarin in human blood and urine was developed. The digoxin-d3 was used as an internal standard. Periplocymarin and digoxin-d3 (IS) were processed with ethyl acetate by liquid-liquid extraction. The chromatographic separation was performed on a Shim-pack XR-ODSIII C18 column with a 7 min gradient elution using methanol-ammonium formate (5 mmol/L) as mobile phase at a flow rate of 0.3 mL/min (65:35, v/v). The detection was performed on a triple quadrupole tandem mass spectrometer using positive-ion mode electrospray ionization in selected reaction monitoring mode. The periplocymarin was well separated from the internal standard. Two calibration curves were linear within the concentration range 0.01-1 μg/mL. The limit of detection and quantification of blood and urine samples were both estimated at 0.005 and 0.01 μg/mL. The interday and intraday precisions, accuracy, and recovery were assessed to verify this method. The results showed that the method was suitable for the determination of periplocymarin in forensic toxicological analysis and clinical diagnosis.

Rapid toxicochemical analysis in phosphide intoxication cases

In recent years, phosphine and metal phosphides intoxications have been observed extremely rarely in clinical practice. Although rare, these intoxications have a severe clinical course, often with unclear clinical presentation at the beginning and possible lethal exit during the first hours or the next several days. Several tests for analysis of phosphide intoxication, based on the classical qualitative semimicroanalysis which do not require complex equipment, are presented and compared in this article. These tests contribute significantly to confirming the toxicology diagnosis and identifying the source. A rapid paper test (adopting the method of Chugh et al. ) has been developed for the purposes of the routine toxicology practice to serve the practicing doctor, as quick and exact diagnostic orientation in cases with unclear history and clinical presentation of the intoxication.

The toxicological diagnosis in suicidal attempt by children and adolescents

The toxicological diagnosis in suicidal attempt by children and adolescents