Clinical Toxicology Research Articles

Historical Aspects of the Development of the State Educational System in the Field of Clinical Toxicology in Russia

Summary. The analysis of the historical development of the state system of training in the field of clinical toxicology showed that the opening of the first specialized departments (centers) served as an impulse for the adoption in the future of appropriate organizational decisions and regulatory documents that led to the creation of the country’s first department of clinical toxicology. In addition, this became possible after the emergence of qualified personnel of clinical toxicologists, as well as scientific and practical areas, primarily general resuscitation and toxicological chemistry, and the achievements of fundamental sciences, new pharmacological and technical means of detoxification of the body, on which basis educational materials of the proper level were formed.An important role for the creation of the Department of Clinical Toxicology was played by the publication by E.A. Luzhnikov, the country’s first textbook on clinical toxicology. The results of the activities of Academician E.A. Luzhnikov in the organization of training in the field of clinical toxicology also contributed to the acquisition of a comprehensive level of knowledge and the expansion of teaching in this direction.However, today, clinical toxicology has not become a basic specialty in the vast majority of medical institutions of higher education, including Moscow, which, in our opinion, hinders the process of training the required number of practical, scientific, and teaching personnel in this area.The choice of clinical bases for training is of fundamental importance, of which multidisciplinary research emergency hospitals or emergency hospitals are optimal.Along with the proven form of teaching in the form of field cycles, further reflection requires the place of distance learning as another approach to expanding the audience of listeners. It is also absolutely necessary to support the teaching process within the framework of continuous professional education, including cooperation with scientific and practical medical societies.The most important component of the learning process is the accumulation of scientific experience in the specialty, to which a decisive contribution is made by the creation of scientific schools on the bases of toxicological subdivisions. Additional opportunities are also provided by the modern formation of the scientific specialty “Toxicology”, which makes it possible to achieve the most qualified examination of the results of scientific research.Conclusion.The development of the state educational system in the field of clinical toxicology in Russia is closely related to its formation as an independent scientific and practical direction in medicine, which has high social significance, and the adoption of the experience gained in the course of educational activities.

A tribute to Pietro Traldi, a scientist and a man who changed my life.

Mass Spectrometry ReviewsEarly View e21752 REMINISCENCE A tribute to Pietro Traldi, a scientist and a man who changed my life Giampietro Frison, Corresponding Author Giampietro Frison giampietro.frison@aulss3.veneto.it DMPO Department, Laboratory of Clinical and Forensic Toxicology, AULSS 3, Venice, Italy Correspondence Giampietro Frison, DMPO Department, Laboratory of Clinical and Forensic Toxicology, AULSS 3, Venice, Italy. Email: giampietro.frison@aulss3.veneto.itSearch for more papers by this author Giampietro Frison, Corresponding Author Giampietro Frison giampietro.frison@aulss3.veneto.it DMPO Department, Laboratory of Clinical and Forensic Toxicology, AULSS 3, Venice, Italy Correspondence Giampietro Frison, DMPO Department, Laboratory of Clinical and Forensic Toxicology, AULSS 3, Venice, Italy. Email: giampietro.frison@aulss3.veneto.itSearch for more papers by this author First published: 16 November 2021 https://doi.org/10.1002/mas.21752Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Early ViewOnline Version of Record before inclusion in an issuee21752 RelatedInformation

Associate Professor Morten Schmidt, Denmark, is the BCPT Young Researcher Nordic Prize winner in Basic & Clinical Pharmacology & Toxicology for 2021.

Associate Professor Morten Schmidt, Denmark, is the BCPT Young Researcher Nordic Prize winner in Basic & Clinical Pharmacology & Toxicology for 2021.

A Bibliometric Analysis of Academic Publications About Intoxication in the Period from 1975 to 2020: A Global and Medical View

Intoxication is still the major cause of morbidity and mortality worldwide. Despite the growing number of global studies about intoxication, comprehensive bibliometric studies are not available in the literature. This study aims to analyze scientific articles about intoxication/poisoning and to evaluate this subject matter from a holistic point of view. Studies about intoxication that were published in the years between 1975 and 2020 were downloaded from the Web of Science (WoS) database and analyzed by bibliometric methods. Spearman’s correlation coefficient was used for correlation analyses. Regression analysis was used to estimate publication trends in the coming years. A total of 32,320 publications about medical research were obtained. Of these publications, 17,508 (54%) were articles. A non-linear growth trend was observed for the number of intoxication articles that have been published in recent years. The most active three institutions were the University of California San Francisco (137), Harvard University (133), and Oxford University (96). Clinical Toxicology was the journal that has published the highest number of articles (683). The most active author was Michael Eddleston (92). The most common subject matters were carbon monoxide, suicide, overdose, organophosphates, toxicology, alcohol, pesticides, epidemiology, children, paraquat, and lead poisoning. In this comprehensive bibliometric study about intoxication, which is a subject matter studied with a growing trend in the literature, we have presented a summary of 17,508 articles. This study can be a beneficial resource for clinicians and scientists by presenting global outputs about intoxication and future prospects and novel subject matters for research

First step in assessment of VipGrade®, a computerized clinical decision system to assess Vipera envenomation grading: a single-center interrater reliability study

Methods We conducted a retrospective review of Vipera spp. snakebite cases registered by the PCC of Bordeaux, France, between January 1, 2018, and December 31, 2020, evaluating the agreement between VipGrade® assessments, toxicologists’ assessments, and current guidelines. Results 133 patients with Vipera aspis snakebites were included. There was 100% agreement in severity grading by PCC guidelines and VipGrade®. However, grading by toxicologists and VipGrade® diverged in 19 cases (85% agreement; κ = 0.80; 95% CI: 0.71 to 0.87). Conclusions The VipGrade® tool’s grading reflects current PCC guidelines, which are authoritative in France, and may allow for a more rapid and standardized determination of management and follow-up of viper-bitten patients. It should be noted, however, that the more complex and dynamic aspects of management are not included in VipGrade®. Its purpose is to supplement, not replace, the advice of the PCC’s clinical toxicologists, and this advice should be sought whenever a viper bite is encountered in clinical practice.

Untargeted metabolomics approaches to improve casework in clinical and forensic toxicology—“Where are we standing and where are we heading?”

AbstractClinical toxicology (CT) and forensic toxicology (FT) represent two disciplines of toxicology dedicated to the qualitative and quantitative analysis and respective interpretation of alcohol, drugs of abuse (DOA), over the counter (OTC), and prescription drugs or poisons, mainly in humans. Analytical challenges, such as the transient occurrence of new psychoactive substances (NPS) on the (il)legal drug market, insufficiently long detection windows of some DOAs, or the lack of objective measures to unambiguously proof sample manipulation as well as interpretative issues, for instance, the difficulty to discriminate occasional users from chronic/addictive ones still require further evaluation and research, though. Metabolomics is a rather new research field, aiming for qualitative, and quantitative analysis of endogenous compounds (small molecules with a molecular weight < 1000 Da) in an organism to identify changes related to a certain stimulus, for example, a drug intake. Over the last years, metabolomics has been established as a valuable tool in different disciplines, including very recently CT and FT. Analytical techniques usually applied include nuclear magnetic resonance and majorly hyphenated high‐resolution mass spectrometry (HR‐MS), similar to the instrumentation used in CT and FT. We will summarize practical considerations for each step of a typical untargeted metabolome workflow (experimental set‐up, sample collection and storage, analysis, data processing, statistics, and identification) in CT and FT, provide an update on the current applications of untargeted metabolome profiling and will critically discuss its benefits or lack thereof within the particular field.This article is categorized under: Toxicology > Analytical Toxicology > Metabolomics Toxicology > New Psychoactive Substances

Skeletal Muscle Relaxants for the Treatment of Myofascial Pelvic Pain and High Tone Pelvic Floor Disorders in Women: A Scoping Review

Study Objective To review the evidence of muscle relaxants and non-injectable drugs with muscle relaxant properties for the treatment of chronic pelvic pain. This includes investigation of whether the concept of skeletal muscle relaxant use for lower back striated muscle strain is a valid construct to apply to the context and treatment of women with chronic pelvic pain due to myofascial and hypertonic muscular dysfunction. The clinical effectiveness, side effects, and toxicology risk of the investigated drugs were characterized. Design A scoping review was conducted in accordance with PRISMA-ScR guidelines and protocols. Online databases were searched using MeSH and subject terms. Articles reporting evidence on skeletal muscle relaxant use were reviewed by two independent reviewers with a third reviewer for any discrepancies. Setting Scoping review. Patients or Participants N/A. Interventions N/A. Measurements and Main Results Comparison studies have not shown any skeletal muscle relaxant to be superior. Skeletal muscle relaxants are divided into two categories: antispastic and antispasmodic agents. Antispastic agents reduce muscle hypertonicity and involuntary jerks associated with neurological disorders. Antispasmodic agents aim to treat striated muscle spasms from musculoskeletal conditions such as low back pain and myofascial pain. Cyclobenzaprine is heavily studied, with demonstrated effectiveness for isolated conditions. Intravaginal diazepam may be beneficial, while other drugs have limited investigation. Considerable knowledge gaps remain regarding appropriate use of these medications in the context of pelvic pain. Conclusion Scant high-quality data exist to support the use of skeletal muscle relaxants for chronic pelvic pain secondary to myofascial and hypertonic muscular dysfunction. Antispastic agents have limited evidence. Antispasmodic agent usage should be based on side-effect profile, patient preference, abuse potential, and possible drug interactions. Future prospective research on antispasmodic agents in women with myofascial dysfunction is necessary to define medication safety, route, dosage, and clinical outcomes. To review the evidence of muscle relaxants and non-injectable drugs with muscle relaxant properties for the treatment of chronic pelvic pain. This includes investigation of whether the concept of skeletal muscle relaxant use for lower back striated muscle strain is a valid construct to apply to the context and treatment of women with chronic pelvic pain due to myofascial and hypertonic muscular dysfunction. The clinical effectiveness, side effects, and toxicology risk of the investigated drugs were characterized. A scoping review was conducted in accordance with PRISMA-ScR guidelines and protocols. Online databases were searched using MeSH and subject terms. Articles reporting evidence on skeletal muscle relaxant use were reviewed by two independent reviewers with a third reviewer for any discrepancies. Scoping review. N/A. N/A. Comparison studies have not shown any skeletal muscle relaxant to be superior. Skeletal muscle relaxants are divided into two categories: antispastic and antispasmodic agents. Antispastic agents reduce muscle hypertonicity and involuntary jerks associated with neurological disorders. Antispasmodic agents aim to treat striated muscle spasms from musculoskeletal conditions such as low back pain and myofascial pain. Cyclobenzaprine is heavily studied, with demonstrated effectiveness for isolated conditions. Intravaginal diazepam may be beneficial, while other drugs have limited investigation. Considerable knowledge gaps remain regarding appropriate use of these medications in the context of pelvic pain. Scant high-quality data exist to support the use of skeletal muscle relaxants for chronic pelvic pain secondary to myofascial and hypertonic muscular dysfunction. Antispastic agents have limited evidence. Antispasmodic agent usage should be based on side-effect profile, patient preference, abuse potential, and possible drug interactions. Future prospective research on antispasmodic agents in women with myofascial dysfunction is necessary to define medication safety, route, dosage, and clinical outcomes.

New Synthetic Cathinones and Phenylethylamine Derivatives Analysis in Hair: A Review.

The analysis of psychoactive substances in hair is of great importance for both clinical and forensic toxicologists since it allows one to evaluate past and continuative exposure to xenobiotics. In particular, a new challenge is represented by new psychoactive substances: Among this new class of drugs of abuse, synthetic cathinone and phenethylamine derivatives are often detected in biological samples. Hence, there is a growing need to develop new analytical procedures or improve old ones in order to conduct evaluations of these emerging substances. This study is a systematic review of all the instrumental and experimental data available in the literature. A total of 32 articles were included in the review. Acidic solvents proved to be the most reliable solutions for extraction. Gas chromatography and liquid chromatography coupled to tandem mass spectrometric and high-resolution mass spectrometric systems represent the majority of the involved instrumental techniques. Sensitivity must be maintained at the pg/mg level to detect any occurrences up to occasional consumption. In total, 23 out of 32 articles reported real positive samples. The most frequently detected substance in hair was mephedrone, followed by butylone, methylone, MDPV, and α-pyrrolidinophenone-type substances.

MIRACLE DRUG UNDER FIRE: HYDROXYCHLOROQUINE OVERDOSE TOXICOKINETICS EXPLORED

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Hydroxychloroquine (HCQ) is a medication used in the treatment of malaria, lupus and rheumatoid arthritis. The drug gained popularity during the early stage of the Coronavirus Disease 2019 (COVID-19) pandemic as an emergency use therapy. It has since been shown in numerous studies that HCQ can actually cause more harm than good. However, its media attention has led to an increase in overdose cases, which can be fatal due to cardiac complications. We present a case of a patient with access to HCQ for COVID-19 prophylaxis who overdosed in a suicide attempt with a favorable outcome. CASE PRESENTATION: A 38-year old Asian American female with no significant history was found 4-6 hours after ingesting approximately 27 grams of oral HCQ. She was admitted to the intensive care for shock and severe hypokalemia (1.7 mmol/L). The pills were obtained from an overseas third party vendor for COVID-19 prophylaxis. Vitals on arrival were BP 60/30 mmHg, HR 66 bpm, temperature 94.9 fahrenheit. Based on previous case reports and studies on chloroquine, the patient was started on an epinephrine and versed drip, including 2 doses of 60mg diazepam. A single dose of activated charcoal was administered. Initial electrocardiogram revealed conduction abnormalities with QT interval of 549ms (629ms with Bazett's correction). The patient received 240 meq of potassium in a span of 25 hour and began to develop hyperkalemia of up to 6.4 mmol/L. After 48 hours, the patient's blood pressure and potassium levels normalized. On hospital day 4, she was successfully extubated with a favorable remaining hospital course. DISCUSSION: The most life threatening sequelae seen in HCQ overdoses are cardiac arrhythmias due to electrolyte imbalances, mainly potassium. Hyperkalemia after initial severe hypokalemia has been observed in numerous case reports of HCQ overdose and thought to be intracellular shifts rather than relative depletion. Thus, caution should be taken in the correction of initial hypokalemia. A review of previous cases shows an inverse relationship between potassium and HCQ levels, as with our case. Reported toxicity half-life ranges between 11.6 and 31 hours. Our case had an approximate peak concentration of 27 µg/ml after 4-6 hours after ingestion with an estimated observed half-life of 27 hours based on recorded concentrations over 45 hours, assuming 1st order elimination. Our patient's hypokalemia began to reverse during the 2nd half-life period which is also consistent with other reported cases. CONCLUSIONS: We believe that during the 2nd half-life, when more than 50% of the drug is eliminated, is the period when correction of hypokalemia should be taken with more caution. While these are only observations based on a few case reports, they can provide more insight on how to better manage electrolyte imbalances which can avoid fatal arrhythmias and circulatory arrest. REFERENCE #1: de Olano, J., Howland, M. A., Su, M. K., Hoffman, R. S., & Biary, R. (2019). Toxicokinetics of hydroxychloroquine following a massive overdose. The American journal of emergency medicine, 37(12), 2264-e5. REFERENCE #2: Jordan, P., Brookes, J. G., Nikolic, G., Le Couteur, D. G., & Le Couteur, D. (1999). Hydroxychloroquine overdose: toxicokinetics and management. Journal of Toxicology: Clinical Toxicology, 37(7), 861-864. REFERENCE #3: Palatnick, W., Meatherall, R., Sitar, D., & Tenenbein, M. (1997). Hydroxychloroquine kinetics after overdose. J Toxicol Clin Toxicol, 35, 496.Miller, D., & Fiechtner, J. (1989). Hydroxychloroquine overdosage. The Journal of rheumatology, 16(1), 142-143. DISCLOSURES: No relevant relationships by Fatima Anjum, source=Web Response No relevant relationships by James Kang, source=Web Response No relevant relationships by Hyfaa Mashaal, source=Web Response No relevant relationships by James Pellegrini, source=Web Response

Place de la salive dans les analyses toxicologiques

AbstractOral fluid testing is of real interest for monitoring drugs of abuse in driving under influence of drugs (DRUID), workplace drug testing, therapeutic drug monitoring, clinical toxicology and postmortem toxicology, possibly in addition to blood or urine. Collection of saliva is easy, non-invasive, and can be performed by non-medical personnel. For the past 20 years, point-of-collection testing devices and confirmation methods more sensitive and specific are more reliable. However, confirmation of positive tests by chromatographic techniques coupled with mass spectrometry remains essential. Interpreting the results must take into account many factors (intra- and inter-individual variabilitie, method of saliva collection, reliability of tests, passive contamination…) that the toxicologist must keep under control.

A SEVER CASE OF CALCIUM CHANNEL BLOCKER TOXICITY REQUIRING HYPERINSULINEMIA EUGLYCEMIA AND LIPID EMULSION TREATMENT

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Calcium channel blocker (CCB) is a significant drug exposure reported to the American Association of Poison centers (1). Medical care of patients poisoned with CCBs can be complex as profound bradycardia and hypotension might be challenging to control, with insufficient evidence on which medical therapy is best (2). Calcium channel blockers directly block calcium L-type channels in the heart and blood vessels leading to hypotension and circulatory collapse in overdose cases. Dihydropyridines are generally less notorious for causing bradycardia than non-dihydropyridine. Amlodipine has a relatively long half-life, and therefore toxicity with amlodipine tends to cause prolonged circulatory collapse (3).This case was particularly challenging since calcium channel blockers were combined with three additional medications, including a benzodiazepine and a GABA receptor agonist (zolpidem). This combination made cardiopulmonary collapse an inevitable consequence. CASE PRESENTATION: A 32-year-old man presented to the emergency department in a stable clinical condition about an hour after intentionally ingesting a total of 300 mg of amlodipine, 1500 mg of bupropion, 3 mg alprazolam, and an unknown amount of zolpidem in a suicidal attempt. Soon after arriving at the emergency room, he started to have slurred speech, and his blood pressure started dropping—treatment initiated with activated charcoal. Subsequently, the patient became more lethargic, requiring emergent sedation, intubation, and mechanical ventilation for airway protection. Additional treatments included hyperinsulinemia euglycemia treatment (HIET), calcium gluconate, sodium bicarbonate, and lipid emulsion.The patient quickly became hemodynamically unstable with a refractory distributive shock requiring high doses of four different vasopressors (norepinephrine, vasopressin, phenylephrine, and epinephrine). Initial laboratory results showed metabolic acidosis (pH of 7.14). Complete blood count and chemistry were unremarkable. Chest x-ray, electrocardiogram, and echocardiogram were essentially normal. After stabilization in the intensive care unit, all vasopressors were successfully weaned off, and the patient was extubated on day 4 of admission. He was transferred out to an inpatient psychiatric unit on day 8 of admission. DISCUSSION: Aside from the initial therapy with intravenous fluids and atropine for bradycardia, there is no agreed-upon algorithms for CCBs toxicity treatment.Hyperinsulinemia euglycemia treatment (HIET) was originally shown to improve survival in dogs poisoned with verapamil in a controlled environment. CONCLUSIONS: Management of calcium channel blocker toxicity is based on maintaining adequate circulation with the use of IV fluids, vasopressors, calcium, high-dose insulin, glucagon, and other therapies that have been documented. REFERENCE #1: Kent R. Olson, Andrew R. Erdman, Alan D. Woolf, Elizabeth J. Scharman, Gwenn Christianson, E. Martin Caravati, Paul M. Wax, Lisa L. Booze, Anthony S. Manoguerra, Daniel C. Keyes, Peter A. Chyka & William G. Troutman (2005) Calcium Channel Blocker Ingestion: An Evidence-Based Consensus Guideline for Out-of-Hospital Management, Clinical Toxicology, 43:7, 797-822. REFERENCE #2: DeWitt CR, Waksman JC. Pharmacology, pathophysiology and management of calcium channel blocker and beta-blocker toxicity. Toxicol Rev. 2004;23(4):223-38. REFERENCE #3: Vimal Upreti, V. R. Ratheesh, Pawan Dhull, and Ajay Handa.Shock due to amlodipine overdose. Indian J Crit Care Med. 2013 Nov-Dec; 17(6): 375–377. DISCLOSURES: No relevant relationships by Matthew Apedo, source=Web Response no disclosure on file for Setana Idriss; No relevant relationships by Mazin Shaikhoun, source=Web Response

Nouvelles applications des systèmes alternatifs de micro-prélèvements

AbstractThe use of Dried Blood Spots (DBS) in the field of biology goes back to the work of Guthrie, initially employed for the neonatal screening of phenylketonuria, and extended since to the screening of a dozen of hereditary diseases. At first qualitative or semi-quantitative, the DBS method was used to the quantification of numerous biomarkers with a major difficulty, due to the lack of the precision of the blood volume collected. Amongst the factors influencing this volume, hematocrit is without any doubt, the most restricting. Two new systems called volumetric: HemaPEN™ and Mitra™ allowed to do without the hematocrit value. They allow to sample with precision the volumes between 2,5µL and 30µL. As the DBS, these new tools have many advantages like the simplicity of storage and transportation. However, the low volumes of blood collected, although compatible with pediatric studies or animal experimentation, require the development of sensitive analytical methods. In general, these methods rely on chromatography coupled to mass spectrometry, validated with a longer sample preparation phase compared to that of conventional samples. Despite their high costs, volumetric systems allowed the emergence of multiple quantitative applications in many fields of medical biology, such as pharmacokinetics, therapeutic drug monitoring, clinical and forensic toxicology.

Illicit Drug Exposures Reported to the Poisons Information Centre Erfurt (2011 to 2020)

Because of significant changes in recent years, cases of illicit drug exposure reported to the Poisons Information Centre (PIC) Erfurt during the last 10 years were investigated. Retrospective analysis of above-mentioned cases from 2011 to 2020 according to substance classes, symptom severity, age groups, and gender. Cases of illicit drug exposure (4,963, 2.8% of all exposures) increased from 316 in 2011 to 614 in 2015, decreased to 514 in 2017, and rose again to 578 in 2019. In 2020, a drop to 549 cases was observed. The ratio of multiple to single drug exposure cases, however, increased from 1.0 to 1.7 in 2020. Cases of exposure to psychostimulants almost doubled from 168 in 2011 to 319 in 2020. Cases of exposure to new psychoactive substances (NPS) rose from 21 in 2011 to 126 in 2015 and fell to 16 in 2020. 320 cases (6.5%) of illicit drug exposures resulted in severe, 1902 cases (38.3%) in moderate and 2139 cases (43.1%) in minor or no symptoms. Age groups mainly involved were adults of middle age (72.7%) and unknown age (12.7%) as well as adolescents (12.1%). Men (69.9%) were more often involved than women (26.9%). Illicit drug exposures reported to the Poisons Information Centre (PIC) Erfurt discontinuously increased from 2011 to 2020 mainly by increase in mixed consumption. The intermittent decrease in 2016 and 2017 was caused by the fall of NPS exposures. Data of substance abuse from PICs could supplement official annual drug reports in aspects of Clinical Toxicology.

North American Congress of Clinical Toxicology (NACCT) Abstracts 2021

North American Congress of Clinical Toxicology (NACCT) Abstracts 2021

Recreational use of GHB and prescribed drugs: the challenge in forensic and clinical toxicology.

The dual nature and the double use of γ-hydroxybutyric acid (GHB) are the fundamentals of its spread as recreational drug. Endo-genously, GHB acts as inhibitory neurotransmitter while exogenously it is administered in the form of sodium oxybate to treat cataplexy and to menage alcohol withdrawal. Illicit GHB is extensively used along with prescribed drugs and drugs of abuse for its euphoric and anabolic effects. Since it has been used as incapacitating agent to perpetrate rapes and commit robberies, GHB represents a social and public health issues. The tight window of detectability in biological matrices and the difficultly to read symptoms of polydrug overdose represent the modern challenges in forensic and clinical toxicology.

Dichloroethane poisoning

Diagnosis and treatment of acute poisoning from dichloroethane remain a very urgent task for clinical toxicology and clinical laboratory diagnostics since it belongs to the group of potent poisonous substances, the poisoning from which is the most severe. Dichloroethane belongs to organochlorine compounds and is a volatile liquid with a specific aromatic odor, very soluble in alcohol and fats. This substance is used not only for industrial purposes but also for household purposes. It is used as a raw material for the production of plastics. It has a fragrant odor, promotes ingestion for intoxication. Dichloroethane is produced in huge quantities and is used in the production of polyvinylchloride and other polymeric materials, fumigants, and adhesives. Death can occur even after taking 10–20 ml of dichloroethane. When ingested, the maximum concentration of substances in the blood is reached after 3–4 hours from the moment of taking, and the rate of absorption increases when taken together with alcohol and fats. Absorbed into the blood, toxic substances accumulate in lipid-rich tissues (brain, liver, omentum, adrenal glands). The toxicity of dichloroethane is due to its metabolism into chloroethanol and monochloroacetic acid, which on the first day determine the clinical picture of a narcotic and depressive effect on the central nervous system and exotoxic shock (at doses exceeding lethal doses), toxic liver dystrophy (on days 2–5), toxic nephropathy, gastrointestinal syndrome. Preventive measures for dichloroethane poisoning include compliance with all safety rules at work and home. Employees of enterprises dealing with this toxic substance must work in rooms with constantly forced ventilation, in industrial filter respirators (gas masks), and protective clothing.

W70. SMALL RNA EXPRESSION PROFILE FROM EXOSOMES OF FIRST EPISODE PSYCHOSIS PATIENTS

Validation of a non-targeted method for urine drug screening (UDS) by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF), and comparison to an established GC–MS method in a hospital setting.217 UDS specimens sent to a quaternary hospital pathology department, were analysed by a CEDIA® immunoassay screen (six drug panels; amphetamines, barbiturates, benzodiazepines, cocaine metabolites, cannabinoids and opiates) on an Abbott Architect instrument. Specimens were subsequently analysed by an established non-targeted qualitative GC–MS method and results compared with a general unknown screening method by LC-QTOF that was under evaluation as a replacement method.42 selected drugs were evaluated; limits of identification ranged from 2 to 100 µg/L and most drugs (n = 39) were stabile for 24 h after preparation. Matrix effects greater than 25% were observed in seven of the selected drugs. 87% of the specimens tested positive to 1 or more drug panels in a CEDIA® screen. A total of 537 positive drug findings were identified by GC–MS compared to 1,267 positive findings by LC-QTOF. On average, each GC–MS screen identified 2.5 ± 1.8 drugs and the LC-QTOF screen identified 5.8 ± 3.2 drugs. No drugs were identified in 11.3% of the GC–MS screens, whereas drugs were detected in 99% of these by the LC-QTOF. In almost all instances, the LC-QTOF screen could provide mass spectrometric confirmatory results of positive immunoassay screens and was able to identify a wider range of additional drugs and drug metabolites.The described general unknown screening (non-targeted, qualitative) LC-QTOF method can detect a larger range of drugs encountered in a hospital setting. The method has been shown to be suitable for comprehensive toxicology screening in a clinical toxicology laboratory.

Urine Drug Screening in the Era of Designer Benzodiazepines: Comparison of Three Immunoassay Platforms, LC-QTOF-MS and LC-MS-MS.

This study investigated the presence of designer benzodiazepines in 35 urine specimens obtained from emergency department patients undergoing urine drug screening. All specimens showed apparent false-positive benzodiazepine screening results (i.e., confirmatory testing using a 19-component liquid chromatography-tandem mass spectrometry (LC-MS-MS) panel showed no prescribed benzodiazepines at detectable levels). The primary aims were to identify the possible presence of designer benzodiazepines, characterize the reactivity of commercially available screening immunoassays with designer benzodiazepines and evaluate the risk of inappropriately ruling out designer benzodiazepine use when utilizing common urine drug screening and confirmatory tests. Specimens were obtained from emergency departments of a single US Health system. Following clinically ordered drug screening using Abbott ARCHITECT c assays and laboratory-developed LC-MS-MS confirmatory testing, additional characterization was performed for investigative purposes. Specifically, urine specimens were screened using two additional assays (Roche cobas c502 and Siemens Dimension Vista) and LC-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) to identify presumptively positive species, including benzodiazepines and non-benzodiazepines. Finally, targeted, qualitative LC-MS-MS was performed to confirm the presence of 12 designer benzodiazepines. Following benzodiazepine detection using the Abbott ARCHITECT, benzodiazepines were subsequently detected in 28/35 and 35/35 urine specimens using Siemens and Roche assays, respectively. LC-QTOF-MS showed the presumptive presence of at least one non-Food and Drug Administration (FDA)-approved benzodiazepine in 30/35 specimens: flubromazolam (12/35), flualprazolam (11/35), flubromazepam (2/35), clonazolam (4/35), etizolam (9/35), metizolam (5/35), nitrazepam (1/35) and pyrazolam (1/35). Two or three designer benzodiazepines were detected concurrently in 13/35 specimens. Qualitative LC-MS-MS confirmed the presence of at least one designer benzodiazepine or metabolite in 23/35 specimens, with three specimens unavailable for confirmatory testing. Urine benzodiazepine screening assays from three manufacturers were cross-reactive with multiple non-US FDA-approved benzodiazepines. Clinical and forensic toxicology laboratories using traditionally designed LC-MS-MS panels may fail to confirm the presence of non-US FDA-approved benzodiazepines detected by screening assays, risking inappropriate interpretation of screening results as false positives.

The comparison of two Chemometric Assisted UV Spectrophotometric Techniques with High-performance Liquid Chromatography Methods for simultaneous determination of three Antiemetic drugs used in Chemotherapy Induced Nausea and Vomiting

This research work was emphasis to adopt green analytical chemistry via development of environmentally friendly methods for simultaneously estimation of drugs used for chemotherapy induced nausea and vomiting (CINV). In these study two multivariate calibration methods namely; Partial least square (PLS) models, Principal component regression (PCR) and RP-HPLC (Reverse phase- high performance liquid chromatography) method were employed for simultaneous assessment of aprepitant (APT), dexamethsone (DEX) and ondansetron (OND) in their market formuations. The chromatographic separation was achieved on Phenomenex Luna C18 column (150mm X 4.6mm in diameter with 5μ particle size) and detection was carried out by UV-Visible detector. The mobile phase comprises a mixture of ethanol and toluene in a ratio of 65:35% v/v, at the flow rate of 1.2ml/ min. The elution was monitored at 225nm and total run time required for separation was 10 min. The retention time of APT, DEX and OND were found to be 4.37 min, 6.57 and 8.11 min respectively. The Applied methods were validated as per ICH guidelines to achieve maximum sensitivity and lowest error. Linearity range for multivariate calibration methods was found to be 5-50μg/mL for APT, DEX and OND and similarly for HPLC methods was found to be 5-30μg/mL,5-30μg/mL and 5-50μg/mL of APT, DEX and OND respectively. A statistical procedure was carried out to find statistical difference among these developed methods. The results revealed that there is no significant difference between two multivariate models and HPLC methods. Therefore, it could be applied as an alternative of HPLC method in quality control laboratories lacking the required facilities for these expensive instruments. Hence, proposed method can also be applied in clinical pharmacy, toxicology and quality control analysis without the interference of commonly encountered dosage form additives.

A Protocol for the Use of Case Reports/Studies and Case Series in Systematic Reviews for Clinical Toxicology.

Introduction: Systematic reviews are routinely used to synthesize current science and evaluate the evidential strength and quality of resulting recommendations. For specific events, such as rare acute poisonings or preliminary reports of new drugs, we posit that case reports/studies and case series (human subjects research with no control group) may provide important evidence for systematic reviews. Our aim, therefore, is to present a protocol that uses rigorous selection criteria, to distinguish high quality case reports/studies and case series for inclusion in systematic reviews.Methods: This protocol will adapt the existing Navigation Guide methodology for specific inclusion of case studies. The usual procedure for systematic reviews will be followed. Case reports/studies and case series will be specified in the search strategy and included in separate sections. Data from these sources will be extracted and where possible, quantitatively synthesized. Criteria for integrating cases reports/studies and case series into the overall body of evidence are that these studies will need to be well-documented, scientifically rigorous, and follow ethical practices. The instructions and standards for evaluating risk of bias will be based on the Navigation Guide. The risk of bias, quality of evidence and the strength of recommendations will be assessed by two independent review teams that are blinded to each other.Conclusion: This is a protocol specified for systematic reviews that use case reports/studies and case series to evaluate the quality of evidence and strength of recommendations in disciplines like clinical toxicology, where case reports/studies are the norm.