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Although therapeutic drug monitoring (TDM) is an important tool in guiding drug dosing for other areas of medicine including infectious diseases, cardiology, psychiatry and transplant medicine, it has not gained wide acceptance in oncology. For imatinib and other tyrosine kinase inhibitors, a flat dosing approach is utilised for management of oral chemotherapy. There are many published studies examining the correlation of blood concentrations with clinical effects of imatinib. The International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT) determined that there was a need to examine the published literature regarding utility of TDM in imatinib therapy and to develop consensus guidelines for TDM based on the available data. This article summarises the scientific evidence regarding TDM of imatinib, as well as the consensus guidelines developed by the IATDMCT.

Objective 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. Methods 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. Results 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 . Conclusions 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.

Background: Benzonatate is a commonly prescribed medication that can be lethal in acute overdose of a small number of capsules. Objective: This was a systematic review to describe the course of severe poisoning and deaths from benzonatate supplemented with the National Poison Data System (NPDS) fatalities module. Methods: The NPDS was queried from 2000 to 2018 for benzonatate fatalities. Pubmed, Cochrane, Embase, and Google Scholar were searched for combinations of benzonatate and “poisoning,” “overdose,” and “toxicity.” References of relevant articles were searched for additional publications. Articles were included if they described the clinical course of at least one patient suffering from benzonatate poisoning and available in English. Dual independent review and extraction were performed. Results: Seventeen cases from NPDS and 19 published reports met the inclusion criteria resulting in 36 cases, mostly (28/36) self-harm ingestions. Most patients were young [17 (11–29), median (IQR)] and female (22). Onset of toxicity was rapid at Conclusion and relevance: Overdose ingestions of benzonatate can cause significant toxicity with a rapid onset. Interventions performed were generally supportive in nature. Duration of directly toxic effects is short, but dramatic with neurologic devastation and resuscitated patients often still have a poor outcome.

Data on cleaner and disinfectant exposure and misuse-related acute intoxications in Italy during SARS-CoV-2 pandemic are still lacking. The aim of the present study was to analyse and describe cleaner and disinfectant-related intoxications during SARS-CoV-2 pandemic in an Italian poison control centre. Data were obtained from the toxicological consultations requested to the Toxicology Unit and Poison Centre, Careggi University Hospital, Florence (Italy). We compared data from January 1st to April 30th of 2019 and 2020. Data concerning probable or acute intoxication from any causative agent in the general population (all age groups), from private individuals or from Regional and National health structures, were included in the analysis. A toxicological evaluation was also performed to calculate the Poisoning Severity Score.In 2019, 451 phone counselling sessions were performed and compared to a total of 410 calls received during the same period of 2020. In both periods, the majority of events occurred in paediatric (0–17 years) and adult (18–65 years) patients, who were mainly exposed to one toxic agent, and intoxications took place principally at home due to domestic accidents. The oral route of intoxication was the most frequently observed one, followed by inhalation of toxic agents, which increased by 4.7% in 2020. In 2020, sanitizers and cleaners were reported in 21.6% of cases compared to 12.5% in 2019. This is the first study describing cleaner and disinfectant-related intoxications in Italy. Our results suggested a possible misuse of these products during the SARS-CoV-2 pandemic, underling the effects of home isolation on mental health and unintentional toxic exposures.

Aim: Multiplexed, high-throughput analysis facilitates therapeutic drug monitoring. 14 drugs with various physico-chemical properties were quantitated in dried blood microsamples. Methods: Analytes were extracted employing eight solvent compositions and seven extraction methods. The applicability of liquid serum, dried serum and dried whole blood calibrators was investigated. Results: High recoveries were attained. Calibration using dried serum yielded lowest total error. Reducing sample hematocrit caused outstanding elevations in recovery of analytes with high polarity or affinity to erythrocytes. 9-day analyte stability was demonstrated. Conclusion: Based on the analysis of spiked samples, multiplexed testing of drugs in dried blood microsamples seems feasible, but with analyte-dependent method performance. Dried serum calibration allows the adaptation of serum-based workflows. Further evaluation using real-life specimens is needed.

Several studies have found aberrant DNA methylation levels in breast cancer cases, but factors influencing DNA methylation patterns and the mechanisms are not well understood. This case–control study evaluated blood methylation level of two repetitive elements and selected breast cancer‐related genes in relation to breast cancer risk, and the associations with serum level of persistent organic pollutants (POPs) and breast cancer risk factors in Greenlandic Inuit. DNA methylation was determined using bisulphite pyrosequencing in blood from 74 breast cancer cases and 80 controls. Using first tertile as reference, the following was observed. Positive associations for ATM in second tertile (OR: 2.33, 95% CI: 1.04; 5.23) and ESR2 in third tertile (OR: 2.22, 95% CI: 0.97; 5.05) suggest an increased breast cancer risk with high DNA methylation. LINE‐1 methylation was lower in cases than controls. In third tertile (OR: 0.42, 95% CI: 0.18; 0.98), associations suggest in accordance with the literature an increased risk of breast cancer with LINE‐1 hypomethylation. Among controls, significant associations between methylation levels and serum level of POPs and breast cancer risk factors (age, body mass index, cotinine level) were found. Thus, breast cancer risk factors and POPs may alter the risk through changes in methylation levels; further studies are needed to elucidate the mechanisms.

The constant emergence of new psychoactive substances is a challenge to clinical and forensic toxicologists who need to constantly update analytical techniques to detect them. A large portion of these substances are synthetic cannabinoids. The aim of this study was to develop a rapid and simple method for the determination of synthetic cannabinoids and their metabolites in urine and blood using gas chromatography-mass spectrometry. The method involves an ultrasound-assisted dispersive liquid-liquid microextraction that implies a rapid procedure, giving excellent extraction efficiencies with minimal use of toxic solvents. This is followed by silylation and analysis with gas chromatography-mass spectrometry. The chromatographic method allows for the separation and identification of 29 selected synthetic cannabinoids and some metabolites. The method was validated on urine and blood samples with the ability to detect and quantify all analytes with satisfactory limits of detection (from 1 to 5 ng/mL), limits of quantification (5 ng/mL), and selectivity and linearity (in the range of 5-200 ng/mL). The developed assay is highly applicable to laboratories with limited instrumental availability, due to the use of efficient and low-cost sample preparation and instrumental equipment. The latter may contribute to enhance the detection of new psychoactive substances in clinical and forensic toxicology laboratories.

Background Many clinical toxicology laboratories receive urine specimens in urine cups that contain point of care (POC) drug testing strips. We conducted this study to evaluate the effect on the stability of commonly measured drugs in the clinical toxicology laboratory when urine is exposed to POC urine drug testing cups. Methods Drug free urine was spiked with 85 drugs that were measured by a validated liquid chromatography mass spectrometry (LCMS) method after exposure to POC urine drug testing cups at ambient and 2–6 °C temperatures. Alterations ≥20% were defined as significant changes in the drugs concentration. Results Concentrations of amitriptyline, cyclobenzaprine, fentanyl, fluoxetine, flunitrazepam, nortriptyline, paroxetine, and sertraline were significantly reduced when urine specimens were stored inside POC urine drug testing cups for 24 h at ambient temperature. Storage of urine in urine chemistry dipsticks reduced the concentration of several drugs. When spiked urine was exposed to an increasing number of POC urine drug testing strips, the concentrations of some drugs were reduced in a dose-dependent manner. The drugs that were absorbed by POC urine drug testing strips were partially back extracted from the strips. Conclusion Exposure of urine specimens to POC urine drug testing strips reduces the concentration of several drugs measured by LCMS method.

BACKGROUND Untargeted data acquisition on high-resolution mass spectrometers (HRMSs) has been used in clinical toxicology for screening and identifying unknown compounds in patient samples. A common modality for untargeted HRMS data acquisition is information-dependent acquisition (IDA), which analyzes the most abundant small molecules within an acquisition cycle. This process can potentially lead to false negatives of clinically relevant compounds at low concentrations. Sequential window acquisition of all theoretical fragment ion spectra (SWATH) has emerged as a method of unbiased, untargeted HRMS data acquisition in which no spectral data are lost. SWATH has yet to be optimized and assessed for use in clinical toxicology. METHOD We developed a variable-window SWATH method (vSWATH) and compared it to IDA by limit of detection studies in drug-supplemented urine (81 compounds) and against a retrospective cohort of 50 clinical urine samples characterized by LC-MS/MS. RESULTS vSWATH had a lower limit of detection than IDA for 33 (41%) drugs and metabolites added into urine samples. Both IDA and vSWATH were equivalent in discovering compounds from clinical urine samples and confirmed 26 additional compounds not previously discovered by targeted LC-MS/MS. Lastly, the unbiased acquisition of spectra in vSWATH allowed for identification of 5 low-abundance compounds missed by IDA. CONCLUSIONS This vSWATH method for clinical toxicology demonstrated equivalent analytical sensitivity and specificity for untargeted drug screening and identification in urine samples. vSWATH provided the additional benefit of collecting all tandem mass spectrometry spectra in a sample, which could be useful in discovering low-abundance compounds not discovered by IDA.

Cocaine (COC) is one of the most widely abused drugs in the world and its sensitive and its reliable measurement in blood is of great importance in the field of forensic and clinical toxicology. Additionally, the determination of COC metabolites such as benzoylecgonine (BZE), cocaethylene (CE), ecgonine methyl ester (EME), and norcocaine (NCOC) are also of complementary diagnostic value. The quantification of COC and metabolites in dried blood spots (DBS) may be an alternative to conventional collection methods with several advantages, including easier, on-site, collection, transportation and storage. In this study, we present a simple and comprehensively validated UPLC–MS/MS assay to measured COC, BZE, EME, NCOC and CE in DBS. The evaluated assay was linear from 5–500 ng mL−1. Precision assays presented CV% of 1.27–6.82, and accuracy in the range of 97–113.78%. Low haematocrit values had a negative impact in the assay accuracy. COC, BE, NCOC and CE measurements can be made reliably in DBS stored for 14 days at room temperature, as well as at −20 °C and 45 °C. All evaluated compounds can be measured in DBS maintained at −20 °C for 14 days. DBS sampling can be used for the clinical evaluation of the exposure to COC, being an alternative for collection, short-term storage and transportation of blood at room and high temperatures.

Background: The assessment and management of patients with QT interval prolongation in poisoning requires an appropriate method of measuring and adjusting the QT interval for the heart rate (HR) in order to decide if the patient is at risk of life-threatening dysrhythmias, notably torsade de pointes (TdP). As the Clinical Toxicology Collaborative (CTC) workgroup reviewed the published literature on drug-induced QT interval prolongation in poisoning, it became obvious that many publications were missing essential data that were necessary to thoroughly assess and compare the evidence. The aim of this guidance document is to identify essential and ideal criteria required when reporting a case of drug-induced QT interval prolongation and/or TdP in poisoning.Methods: We employed a mixed methods approach as follows. Initially, we reviewed 188 cases of available published case reports and series in the literature regarding drug-induced QT interval prolongation and/or TdP in poisoning as the first step to another project. Common features and deficiencies were identified. Given the large gaps in reporting quality, we conducted an iterative consultative process involving all 23 members of the CTC to identify essential and ideal criteria to analyse publications of QT interval prolongation in poisoning. A priori standards were developed for acceptance or rejection of individual criteria.Results: Survey response was 100%. A minimum set of essential criteria for reporting cases of QT interval prolongation and drug-induced TdP in overdose setting are provided and a 35-item checklist is presented.Conclusions: We report a QT reporting checklist to ensure published case reports and series describing drug-induced QT interval prolongation in poisoning can contribute to the fund of knowledge of QT interval prolongation, TdP and other malignant dysrhythmias.

5-Fluorouracil (5-FU) is dosed by body surface area, a practice unable to reduce the interindividual variability in exposure. Endorsed by the International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT), we evaluated clinical evidence and strongly recommend TDM for the management of 5-FU therapy in patients with colorectal or head-and-neck cancer receiving common 5-FU regimens. Our systematic methodology provides a framework to evaluate published evidence in support of TDM recommendations in oncology.

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 pa...

Sodium hypochlorite is used as a bleaching and disinfecting agent and is commonly found in household bleach.The objective is to review critically the epidemiology, mechanisms of toxicity, clinical features, diagnosis, and management of hypochlorite poisoning.PubMed was searched from January 1950 to June 2018 using the terms "Hypochlorite", "Sodium Hypochlorite", "Sodium Oxychloride", "Hypochlorous Acid", "Bleach", "Chlorine Bleach", in combination with the keywords "poisoning", "poison", "toxicity", "ingestion", "adverse effects", "overdose", and "intoxication". In addition, bibliographies of identified articles were screened for additional relevant studies including non-indexed reports. Non-peer-reviewed sources were also included. These searches produced 110 citations which were considered relevant.There is limited information regarding statistical trends on world-wide poisoning from sodium hypochlorite. In the United States of America, poison control center data have shown that enquiries regarding hypochlorite bleaches have ranged from 43,000 to 46,000 per year over the period 2012-2016. Mechanisms of toxicity: Hypochlorite's potential to cause toxicity is related to its oxidizing capacity and the pH of the solution. Toxicity arises from its corrosive activity upon contact with mucous membranes and skin. Features following ingestion: While small accidental ingestions are very unlikely to cause clinically significant toxicity, large ingestions may cause corrosive gastrointestinal injury and systemic effects, including metabolic acidosis, hypernatremia, and hyperchloremia. Features following dental exposure: Hypochlorite is used extensively by dentists for cleaning root canals and is safe if the solution remains within the root canal. Extrusions into the periapical area can result in severe pain with localized large and diffuse swelling and hemorrhage. Features following skin exposure: Prolonged or extensive exposure may cause skin irritation and damage to the skin or dermal hypersensitivity. Such exposures can result in either immediate or delayed-type skin reactions. High concentration solutions have caused severe chemical skin burns. Features following inhalation: Although there are only limited data, inhalation of hypochlorite alone is likely to lead to no more than mild irritation of the upper airways. Features following ocular exposure: Corneal injuries from ocular exposure are generally mild with burning discomfort and superficial disturbance of the corneal epithelium with recovery within 1 or 2 days. With higher concentration solutions, severe eye irritation can occur.The diagnosis can typically be made on the basis of a careful history, including details of the specific product used, its hypochlorite concentration, and the amount involved. As hypochlorite bleach produces a characteristic smell of chlorine, this may provide a diagnostic clue. In severe cases, corrosive injury is suggested on presentation because of hypersalivation, difficulty swallowing, retrosternal pain or hematemesis.Symptom-directed supportive care is the mainstay of management. Gastrointestinal decontamination is not beneficial. Local corrosive injury is the major focus of treatment in severe cases. Fiberoptic endoscopy and CT thorax/abdomen are complimentary and have been shown to be useful in corrosive injuries in assessing the severity of injury, risk of mortality and risk of subsequent stricture formation and should be performed as soon as possible after ingestion. Dental periapical extrusion injuries should be left open for some minutes to allow bleeding through the tooth and to limit hematoma development in tissue spaces. Once the bleeding has ceased, the canal can be dressed with non-setting calcium hydroxide and sealed coronally.Accidental ingestion of household bleach is not normally of clinical significance. However, those who ingest a large amount of a dilute formulation or a high concentration preparation can develop severe, and rarely fatal, corrosive injury so prompt supportive care is essential as there is no specific antidote. Treatment primarily consists of symptom-directed supportive care.

Dried blood spot (DBS) analysis has been introduced more and more into clinical practice to facilitate Therapeutic Drug Monitoring (TDM). To assure the quality of bioanalytical methods, the design, development and validation needs to fit the intended use. Current validation requirements, described in guidelines for traditional matrices (blood, plasma, serum), do not cover all necessary aspects of method development, analytical- and clinical validation of DBS assays for TDM. Therefore, this guideline provides parameters required for the validation of quantitative determination of small molecule drugs in DBS using chromatographic methods, and to provide advice on how these can be assessed. In addition, guidance is given on the application of validated methods in a routine context. First, considerations for the method development stage are described covering sample collection procedure, type of filter paper and punch size, sample volume, drying and storage, internal standard incorporation, type of blood used, sample preparation and prevalidation. Second, common parameters regarding analytical validation are described in context of DBS analysis with the addition of DBS-specific parameters, such as volume-, volcano- and hematocrit effects. Third, clinical validation studies are described, including number of clinical samples and patients, comparison of DBS with venous blood, statistical methods and interpretation, spot quality, sampling procedure, duplicates, outliers, automated analysis methods and quality control programs. Lastly, cross-validation is discussed, covering changes made to existing sampling- and analysis methods. This guideline of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology on the development, validation and evaluation of DBS-based methods for the purpose of TDM aims to contribute to high-quality micro sampling methods used in clinical practice.

Monoclonal antibodies (Mabs) have become key drugs in cancer treatment, either as targeted therapies or more recently as immune checkpoint inhibitors (ICIs). The fact that only some patients benefit from these drugs poses the usual question in the field of onco‐hematology: that of the benefit of individual dosing and the potential of therapeutic drug monitoring (TDM) to carry out this individualization. However, Mabs present unique pharmacological characteristics for TDM, and the pharmacokinetic–pharmacodynamic relationship observed should be interpreted differently than that observed for conventional drugs and small molecules. This pharmacology practice review has been summarized from a public debate between the authors at the International TDM and Clinical Toxicology meeting in Banff, 2020, regarding the potential roles of TDM in the Mab/ICI setting., This pharmacology practice review has been summarized from a public debate between the authors at the International therapeutic drug monitoring (TDM) and Clinical Toxicology meeting in Banff, 2020, regarding the potential roles of TDM in the Monoclonal Antibody/Checkpoint Inhibitors setting.

Snakebite envenoming is predominantly an occupational disease of the rural tropics, causing death or permanent disability to hundreds of thousands of victims annually. The diagnosis of snakebite envenoming is commonly based on a combination of patient history and a syndromic approach. However, the availability of auxiliary diagnostic tests at the disposal of the clinicians vary from country to country, and the level of experience within snakebite diagnosis and intervention may be quite different for clinicians from different hospitals. As such, achieving timely diagnosis, and thus treatment, is a challenge faced by treating personnel around the globe. For years, much effort has gone into developing novel diagnostics to support diagnosis of snakebite victims, especially in rural areas of the tropics. Gaining access to affordable and rapid diagnostics could potentially facilitate more favorable patient outcomes due to early and appropriate treatment. This review aims to highlight regional differences in epidemiology and clinical snakebite management on a global scale, including an overview of the past and ongoing research efforts within snakebite diagnostics. Finally, the review is rounded off with a discussion on design considerations and potential benefits of novel snakebite diagnostics.

Quantum dots (QDs) have been exploited for a range of scientific applications where the analytes can be expected to have significant photoluminescent properties. Previously, the applications of QDs as nanosensors for the detection of toxics in biospecimens, especially in cases of poisoning, have been discussed. This review focuses on the applications of QDs as biosensors for the detection of phytotoxins, vertebrate and invertebrate toxins, and microbial toxins present in biospecimens. Further, the role of QDs in the measurement of biochemical parameters of patient/victim as an indirect method of poison detection is also highlighted.

Aims Huntington's disease (HD) is a neurodegenerative disease with cognitive, motor and psychiatric symptoms. Toxic accumulation of misfolded mutant huntingtin protein induces mitochondrial dysfunction, leading to a bioenergetic insufficiency in neuronal and muscle cells. We evaluated the safety, pharmacokinetics and pharmacodynamics of SBT-020, a novel compound to improve mitochondrial function, in a 2-part study in early stage HD patients.Methods Part 1 consisted of 7-day multiple ascending dose study to select the highest tolerable dose for Part 2, a 28-day multiple dose study. Mitochondrial function was measured in the visual cortex and calf muscle, using phosphorous magnetic resonance spectroscopy, and in circulating peripheral blood mononuclear cells.Results Treatment-emergent adverse events were mild and more present in the SBT-020 group. Injection site reactions occurred in 91% in Part 1 and 97% in Part 2. Mitochondrial function in calf muscle, peripheral blood mononuclear cells or visual cortex was not changed overall due to treatment with SBT-020. In a posthoc analysis, patients with a higher degree of mitochondrial dysfunction (below the median [ increment psi(m) < 3412 and tau PCr > 42.5 s]) showed more improvement than patients with a relatively lower level of mitochondrial dysfunction.Conclusion SBT-020 was safe at all doses, but no significant differences in any of the pharmacodynamic measurements between the treatment groups and placebo group could be demonstrated. The data suggest that the better than expected mitochondrial function in our patient population at baseline might explain the lack of effect of SBT-020.

Dear Editor,Recently, Clinical Toxicology published four reports on the intentional sodium nitrite poisoning in the United States [1–4]. These studies provided interesting epidemiological trends re...

Dear editor,The letter by Goodnough et al. highlights an important area of clinical toxicology, the aim to improve the management of paracetamol overdose. During and beyond the COVID-19 pandemic, h...

Azide is a highly toxic chemical agent to human being. Accidental, but also intentional exposure to azide occurs. To be able to confirm azide ingestion, we developed a method to identify and quantify azide in biological matrices. Cyanide was included in the method to evaluate suggested in vivo production of cyanide after azide ingestion. Azide in biological matrices was first derivatized by propionic anhydride to form propionyl azide. Simultaneously, cyanide was converted into hydrogen cyanide. After thermal rearrangement of propionyl azide, ethyl isocyanate was formed, separated together with hydrogen cyanide by gas chromatography (GC) and detected using a nitrogen phosphorous detector (NPD). The method was linear from 1.0‐100 µg/mL for both analytes, and azide was stable in human plasma at −20°C for at least 49 days. Azide was measured in the gastric content of two cases of suspected azide ingestion (case 1:1.2 mg/mL, case 2:1.5 mg/mL). Cyanide was only identified in the gastric content of case 1 (approximately 1.4 µg/mL). Furthermore, azide was quantified in plasma (19 µg/mL), serum (24 µg/mL), cell pellet (21 µg/mL) and urine (3.0 µg/mL) of case 2. This method can be used to confirm azide and cyanide exposure, and azide concentrations can be quantified in several biological matrices.

Three major classes of natural products (NPs) for medicinal purposes or improving wellbeing are generally available in the US: conventional drugs of herbal origin, botanical drugs, and dietary supplements (DSs). Consumer consumption of DSs is growing annually. The U.S. FDA regulates conventional and botanical drugs for safety and efficacy; however, DSs are minimally regulated.This article will: i) highlight the importance of NP as a significant source of prescription drugs; ii) discuss differences in the regulation of conventional drugs of NP product, botanical drugs, and DSs; iii) discuss the safety and efficacy of DSs and iv) make recommendations for improvement of safety for minimally regulated NPs.Toxicities associated with the use of NPs, including vitamins and DSs, are mainly due to excessive use and interactions with conventional drug(s) and may represent challenges for clinicians. Conventional and botanical-based prescription drugs are rarely associated with unknown toxicities. However, DSs are minimally regulated and can produce severe adverse effects. We believe that clinical pharmacologists can have a role in developing criteria for DS safety analysis. There is also the potential for a standardized NP stewardship program(s) and the development of NP policies and practices nationally and globally.

Background: Recent clinical trials demonstrate the benefits of the antifibrinolytic drug tranexamic acid but its pharmacokinetics remain to be investigated more in depth. Although pharmacokinetics studies are usually performed with plasma, volumetric absorptive microsampling devices allow us to analyze dried whole blood samples with several advantages. Materials & methods: High-sensitivity LC–MS/MS methods for the quantification of tranexamic acid in human whole blood using liquid samples or dry samples on volumetric absorptive microsampling devices were developed and validated based on International Association from Therapeutic Drug Monitoring and Clinical Toxicology, European Medicines Agency and US Food and Drug Administration guidance. Conclusion: The method performances were excellent across the range of clinically relevant concentrations. The stability of tranexamic acid in blood samples stored up to 1 month at +50°C was demonstrated. The methods’ suitability was confirmed with clinical samples.

In order to assess the significance of drug/substance levels measured in intensive care medicine and clinical and forensic toxicology as well as for therapeutic drug monitoring, it is essential that a comprehensive collection of data is readily available. We revisited and expanded our 2012 compilation of therapeutic and toxic plasma concentration ranges as well as half-lives of now more than 1100 drugs and other xenobiotics.Data have been abstracted from original papers, text books, and previous compilations and have been completed with data collected in our own forensic and clinical toxicology laboratories. We compiled the data presented in the table and the corresponding annotations over the past 30+ years. A previous compilation was completely double-checked, revised, and updated, if necessary. In addition, more than 200 substances, especially drugs who have been introduced since 2012 to the market as well as illegal drugs and other xenobiotics which became known to cause intoxications were added. We carefully referenced all data. Moreover, the annotations providing details were updated and revised, when necessary.For more than 1100 drugs and other xenobiotics, therapeutic (“normal”) and, if data was available, toxic, and comatose-fatal plasma/blood concentrations as well as elimination half-lives were compiled in a table.In case of intoxications, the blood concentration of the substance and/or metabolite better predicts the clinical severity of the case when compared to the assumed amount and time of ingestion. Comparing and contrasting the clinical case against the data provided, including the half-life, may support the decision for or against further intensive care. In addition, the data provided are useful for the therapeutic monitoring of pharmacotherapies, to facilitate the diagnostic assessment and monitoring of acute and chronic intoxications as well as to support forensic and clinical expert opinions.

New psychoactive substances (NPS) have emerged worldwide in recent years, posing a threat to public health and a challenge to drug policy. NPS are usually derivatives or analogues of"classical" recreational drugs designed to imitate their effects while circumventing regulations. This article provides an overview of benefits and limitations of analytical screening in managing patients presenting with acute NPS toxicity. NPS typically cannot be analytically identified with the usual immunoassay tests. In order to detect NPS using an immunoassay, antibodies specifically binding to the new structures would have to be developed, which is complicated by the rapid change of the NPS market. Activity-based assays could circumvent this problem since no prior knowledge on the substance structure is necessary. However,"classical" recreational drugs activating the same receptors could lead to false positive results. Liquid or gas chromatography coupled with mass spectrometry is a valuable NPS analysis tool, but its costs (e.g. equipment), run time (results usually within hours vs. minutes in case of immunoasssays) and the need for specialized personnel hinder its use in clinical setting, while factors such as lack of reference standards can pose further limitations. Although supportive measures are sufficient in most cases for adequate patient management, the detection and identification of NPS can contribute significantly to public health and safety in cases of e.g. cluster intoxications and outbreaks, and to the investigation of these novel compounds' properties. However, this requires not only availability of the necessary equipment and personnel, but also collaboration between clinicians, authorities and laboratories.

Aims Presentations of intoxicated patients to hospital are frequent and increasing. We aimed to review the existing evidence that the presence of inpatient clinical toxicology services reduces use of resources without impacting on the care of these patients. Methods We conducted a literature search using the Cochrane Library, PubMed, and Embase for articles that measured length of stay (and other outcomes) for the target population, with toxicology services as an intervention. The articles were reviewed with respect to the ROBINS-I tool. Results Seven relevant articles were identified. Six of these studies demonstrated reduced hospital length of stay for intoxicated patients in hospitals with inpatient toxicology services. None of the articles demonstrated a detriment in morbidity or mortality. There were also improvements in other resource-related outcomes. Conclusions The presence of inpatient toxicology services appears to improve resource utilization, in reduction of length of stay, as well as a number of other related outcomes. It does this without compromising on patient morbidity or mortality. Thus, it should be considered as a potential model of care for future toxicology services, especially with current trends of increasing demand for service efficiency.

Background: Modified-release (MR) paracetamol is available in many countries as 665 mg tablets of which 69% is MR and 31% is immediate release. There are concerns that MR paracetamol overdose has higher rates of liver injury despite standard treatment algorithms. The objective of this study was to describe the clinical characteristics and outcomes of acute MR paracetamol overdose. Methods: Prospective observational study, recruiting patients from January 2013 to June 2017, from five clinical toxicology units and calls to two Poisons Information Centres in Australia. Included were patients >14 years who ingested ≥10 g or 200 mg/kg (whichever is less) of MR paracetamol. Data collected included demographics, ingestion history, pathology results, treatments, and outcomes including hepatotoxicity (ALT >1000 U/L). Results: In total, 116 patients were recruited, 85(73%) were female. The median dose ingested was 32 g (IQR: 20–49 g) and median time to presentation was 3 h (IQR: 2–9 h). 78(67%) had an initial paracetamol concentration above the nomogram line (150 mg/L at 4 h). A further 12(10%) crossed the nomogram after repeat paracetamol measurements, of which five crossed after two non-toxic levels 4 h apart. Six had a double paracetamol peak, in three occurring >24 h post-ingestion. 113(97%) received acetylcysteine of which 67 received prolonged treatment beyond the standard 21 h. This was because of an elevated paracetamol concentration at the completion of acetylcysteine in 39 (median paracetamol concentration 25 mg/L, IQR: 16–62 mg/L). 21 (18%) developed hepatotoxicity, including six treated within 8 h of ingestion. Activated charcoal and double doses of acetylcysteine did not significantly decrease the risk of hepatotoxicity. Conclusions: Drug regulatory authorities are considering restrictions on MR paracetamol preparations. Following an acute MR paracetamol overdose, this study found that many patients had a persistently elevated paracetamol concentrations, many required prolonged treatment and some developed liver injury despite early acetylcysteine treatment. Furthermore, activated charcoal and increased acetylcysteine did not appear to significantly alter the risk of liver injury. Hence, research into better treatment strategies is required. Trial registration: Australian Toxicology Monitoring (ATOM) Study – Australian Paracetamol Project: ACTRN12612001240831 (ANZCTR) Date of registration: 23/11/2012.

Modafinil is used because of its wakefulness-promoting properties for treatment of diseases associated with extreme sleepiness (i.e., narcolepsy). Additionally, it is misused as a "cognitive enhancer" to increase alertness and to improve concentration. We present modafinil concentrations in serum samples in five cases of our routine work measured by high-performance liquid chromatography coupled with a photo diode array detector after solid-phase extraction. One sample was analyzed for clinical toxicology purposes. The other four were investigated for the police: three cases of driving under the influence of drugs and one case of bodily harm. Sample preparation consisted of solid-phase extraction using Bond Elut® C18 columns. Papaverine was used as internal standard. Chromatographic separation was carried out using a Polaris C18-A column in an isocratic run. Wavelengths used for UV-detection were 220 nm for modafinil and 239 nm for the internal standard, respectively. The method was validated with a reduced validation design for rare analytes. A six-point-calibration from 0.5 to 5.0 mg/L, covering the therapeutic range (0.9-3.3 mg/L), was used for quantification. Concentrations in serum were in the range of 1.3 to ~34 mg/L (median: 3.6 mg/L; mean: 9.0 mg/L). To our knowledge, there are only few publications concerning the serum concentrations of modafinil in cases of (suspected) misuse, forensic cases or intoxications. In our discussion, the serum concentrations we determined are compared with the levels described in the literature so far.

In the last few years an increasing number of new psychoactive substances (NPS), with different chemical structures (of which 37% are stimulants), have been released into the illicit drug market. Their detection and identification in biological samples is hence of great concern. The aim of this work was to develop a high-throughput and rapid method for the determination of different classes of stimulants (amphetamine-type stimulants, cathinones, phenethylamines and ketamine analogues) from blood and urine samples using GC–MS. The proposed method allows the almost simultaneous derivatization and extraction of analytes from biological samples in a very short time, by using hexyl chloroformate as derivatization agent. The extraction of analytes was performed by Dispersive Liquid Liquid Microextraction (DLLME), a very rapid, cheap and efficient extraction technique that employs microliter amounts of organic solvents. The chromatographic method allowed for the separation of 26 stimulants including positional isomers (3-MMC and 4-MMC). The method was validated on urine and blood samples with the ability to detect and quantify all analytes with satisfactory limits of detection (LODs) ranging between 1 and 10 ng/mL, limits of quantification (LOQs) between 2 and 50 ng/mL, selectivity and linearity (5–1000 ng/mL). The method was then applied to real samples from forensic cases, demonstrating its suitability for the screening of a wide number of stimulants in biological specimens.

Objectives: Yew plant materials contain highly toxic taxine alkaloids. Serious ingestions can result in life-threatening toxicity. The purpose of this article is to summarize the literature on the treatment of acute yew poisoning. Data Sources: PubMed (January 1946 to November 2017) was searched using the search terms “taxus/po”. EMBASE (1980 to November 2017) was searched using the search terms “taxus/to” and “yew.mp.” Web of Science (1945 to November 2017) was searched using the text words taxus, taxine, and yew. Study Selection and Data Extraction: Available English language articles involving case reports, epidemiology, treatment, and outcomes were included. Data Synthesis: Although not uncommon, unintentional yew poisoning rarely results in significant morbidity or mortality. A total of 26 case reports of yew poisoning were evaluated along with 4 case series articles (totaling 22 additional cases). Only 4 of the 48 total cases (8%) were accidental poisonings, the rest being deliberate ingestions. In 20 patients (42%), it resulted in fatalities. Severe, acute yew poisoning results in symptomatology largely resistant to pharmacotherapy intervention. Conclusions: Most nonintentional ingestions of yew plant constituents are asymptomatic and require little intervention. Severe poisoning can result in life-threatening cardiac toxicity and require aggressive supportive care. Therapeutic interventions, such as sodium bicarbonate, digoxin immune fab, and hemodialysis that have been utilized in case studies and case series in the literature have little proven benefit. Extracorporeal life support should be considered in severe yew poisoning.

To the EditorWe appreciate the comments of Megarbane et al. regarding our previous article published in CLINICAL TOXICOLOGY [1]. They add interesting data on patients with cocaine intoxication that...

Background and aim Aim of this review is to describe the role of clinical toxicology in the context of acute medicine. A special focus is put on antidotes and important aspects of diagnosis and therapy of acute intoxications. The data of the annual report of GIZ-Nord Poisons Centre is analyzed concerning the following aspects: what intoxications are relevant in acute medicine, are there special aspects in therapy, e.g. antidotes, and what antidotes are relevant? More over intoxication-related fatalities are analyzed. Results and conclusion In 2015 the poisons centre was consulted in 33,000 cases of acute intoxications. The most important groups are drugs (e.g. antidepressants, beta blockers and calcium channel blockers), chemical products (e.g. products containing surfactant, corrosive substances and toxic alcohols like methanol), plants and recreational drugs. Intoxications are relevant in acute medicine. Some substances can cause fatal intoxications. Important antidotes are naloxone for opiods, acetylcystein for paracetamol, fomepizole and ethanol for toxic alcohols and diazepam for intoxications caused by chloroquine.

Because of its superior sensitivity and specificity, multianalyte high-performance liquid chromatography coupled with tandem mass spectrometry has become the gold standard in clinical toxicology. Although several qualitative and quantitative liquid chromatography coupled with tandem mass spectrometry assays on various mass spectrometry platforms have been described in the literature, most methods either analyze only a limited number of compounds and/or require tedious and time-consuming sample preparation.A major challenge in urine toxicology screening is the minimization of false-negative and false-positive results. This was addressed by screening for a comprehensive panel of 136 compounds of importance for pain and drug addiction clinics, using high-end, high-sensitivity, fast-scanning mass spectrometry in combination with simultaneous structural confirmation based on ion ratios. The assay was validated and successfully participated in proficiency challenges.The assay met all predefined acceptance criteria. The lower limit of quantifications ranged from 10 to 100 ng/mL. Interday trueness and imprecisions ranged from 73.8% to 116.2% and 2.4%-20.0%, respectively. The total assay run time was 10 minutes.We developed and successfully validated a robust, sensitive, and specific liquid chromatography coupled with tandem mass spectrometry-based urine toxicology screening platform that allows for the addition of drugs to quickly adjust to new clinical needs. To date, more than 3000 clinical samples have successfully been analyzed. Our results also indicated that such a quantitative multianalyte assay is pushing against the limits of current fast-scanning MS/MS instrumentation and that the number of analytes and their internal standards must be balanced with acceptable sensitivity, reproducibility, structural confirmation, and the ability to reliably quantify, all of which was achieved.

Paracetamol is commonly taken in overdose, with increasing concerns that those taking "massive" overdoses have higher rates of hepatotoxicity and may require higher doses of acetylcysteine. The objective was to describe the clinical characteristics and outcomes of "massive" (≥ 40 g) paracetamol overdoses.Patients were identified through the Australian Paracetamol Project, a prospective observational study through Poisons Information Centres in NSW and Queensland, over 3 and 1.5 years, respectively, and retrospectively from three clinical toxicology unit databases (over 2.5 to 20 years). Included were immediate-release paracetamol overdoses ≥ 40 g ingested over ≤ 8 h. Outcomes measured included paracetamol ratio[defined as the ratio of the first paracetamol concentration taken 4-16 h post-ingestion to the standard (150 mg/L at 4 h) nomogram line at that time] and hepatotoxicity (ALT1000 U/L).Two hundred paracetamol overdoses were analysed, reported median dose ingested was 50 g (interquartile range (IQR): 45-60 g) and median paracetamol ratio 1.9 (IQR: 1.4-2.9, n = 173). One hundred and ninety-three received acetylcysteine at median time of 6.3 h (IQR: 4-9.3 h) post-ingestion. Twenty-eight (14%) developed hepatotoxicity, including six treated within 8 h of ingestion. Activated charcoal was administered to 49(25%), at median of 2 h post-ingestion (IQR:1.5-5 h). Those receiving activated charcoal (within 4 h of ingestion), had significantly lower paracetamol ratio versus those who did not: 1.4 (n = 33, IQR: 1.1-1.6) versus 2.2 (n = 140, IQR: 1.5-3.0) (p .0001) (paracetamol concentration measured ≥ 1 h after charcoal). Furthermore, they had lower rates of hepatotoxicity [unadjusted OR: 0.12 (95% CI:0.001-0.91); adjusted for time to acetylcysteine OR: 0.20 (95%CI: 0.002-1.74)]. Seventy-nine had a paracetamol ratio ≥2, 43 received an increased dose of acetylcysteine in the first 21 h; most commonly a double dose in the last bag (100 to 200 mg/kg/16 h). Those receiving increased acetylcysteine had a significant decrease risk of hepatotoxicity [OR:0.27 (95% CI: 0.08-0.94)]. The OR remained similar after adjustment for time to acetylcysteine and paracetamol ratio.Massive paracetamol overdose can result in hepatotoxicity despite early treatment. Paracetamol concentrations were markedly reduced in those receiving activated charcoal within 4 h. In those with high paracetamol concentrations, treatment with increased acetylcysteine dose within 21 h was associated with a significant reduction in hepatotoxicity.

In recent years, there have been a number of significant developments in toxicology within clinical laboratories, both with the available instrumentation and in the range of compounds abused by the drug using communities. There have also been developments in the regulation of forensic science in the UK which may in time impact clinical toxicology. This review is designed to provide an update of these changes within toxicology to the more general pathology laboratory audience. For detailed information in specific areas, the reader is referred to the references in the text. In the preparation of this review, the references held by the author as part of his practice of an analytical toxicologist in the NHS were supplemented by a full literature search in Medline and Embase and a review of pertinent UK and European Governments and regulatory agency websites for recent documentation.

In November 2015, a neurologist in the Boston, Massachusetts, area reported four cases of an uncommon amnestic syndrome involving acute and complete ischemia of both hippocampi, as identified by magnetic resonance imaging (MRI), to the Massachusetts Department of Public Health (MDPH) (1). A subsequent e-mail alert, generated by the Massachusetts Board of Registration in Medicine and sent to relevant medical specialists (including neurologists, neuroradiologists, and emergency physicians), resulted in the identification of 10 additional cases that had occurred during 2012-2016. All 14 patients (mean and median age = 35 years) had been evaluated at hospitals in eastern Massachusetts. Thirteen of the 14 patients underwent routine clinical toxicology screening at the time of initial evaluation; eight tested positive for opioids, two for cocaine, and two for benzodiazepines. Apart from sporadic cases (2-6), this combination of clinical and imaging findings has been reported rarely. The apparent temporospatial clustering, relatively young age at onset (19-52 years), and associated substance use among these patients should stimulate further case identification to determine whether these observations represent an emerging syndrome related to substance use or other causes (e.g., a toxic exposure).

Although both the prevalence of asthma and the prescription drug use, notably the opiate analgesic class, epidemics are increasing, there is a complex interplay between both disorders, with both protective and exacerbating factors involved in the effect of opiates on asthma pathogenesis and clinical severity. This review examines the airway effects, both immunologic and neurologic, of opiates, which may interact and result in protection or exacerbation of asthma.

Methylmercury (MeHg) is a highly neurotoxic compound to which human populations are exposed via fish consumption. Once in cells, MeHg actively binds thiols and selenols, interfering with the activity of redox enzymes such as thioredoxin (Trx) and the selenoenzyme thioredoxin reductase (TrxR) which integrate the thioredoxin system. In fact, it has been shown that inhibition of this system by MeHg is a critical step in the unfolding of cell death. Current clinical approaches to mitigate the toxicity of MeHg rely on the use of chelators, such as meso-2,3-dimercaptosuccinic acid (DMSA) which largely replaced British anti-Lewisite or 2,3-dimercapto-1-propanol (BAL) as the prime choice. However, therapeutic efficacy is limited and therefore new therapeutic options are necessary. In this work, we evaluated the efficacy of a macrocyclic chelator, 1-thia-4,7,10,13-tetraazacyclopentadecane ([15]aneN4S), in preventing MeHg toxicity, namely by looking at the effects over relevant molecular targets, i.e., the thioredoxin system, using both purified enzyme solutions and cell experiments with human neuroblastoma cells (SH-SY5Y). Results showed that [15]aneN4S had a similar efficacy to DMSA and BAL in reversing the inhibition of MeHg over purified TrxR and Trx by looking at both the 5,5&prime, dithiobis(2-nitrobenzoic acid) (DTNB) reduction assay and insulin reduction capability. In experiments with cells, none of the chelating agents could reverse the inhibition of TrxR by MeHg, which corroborates the high affinity of MeHg to the selenol in TrxR active site. [15]aneN4S and BAL, unlike DMSA, could prevent inhibition of Trx, which allows the maintenance of downstream functions, although BAL showed higher toxicity to cells. Overall these findings highlight the potential of using [15]aneN4S in the treatment of MeHg poisoning and encourage further studies, namely in vivo.

Study objective We studied the severity of poisoning after exposure to low to moderate and high doses of 4-bromo-2,5-dimethoxyphenethylamine (2C-B). Methods Patients for whom the Dutch Poisons Information Centre was consulted for 2C-B exposure from 2016 to 2018 were included in a prospective cohort study. Data were collected through telephone interviews with the physician or patient. Patients were categorized according to the reported 2C-B dose: low to moderate (up to 20 mg), high (greater than 20 mg), or unknown. Presence of 2C-B was analyzed in leftover drug and biological samples with liquid/gas chromatography–mass spectrometry. The severity of poisoning was graded with the Poisoning Severity Score. Results We included 59 patients, of whom 32 could be followed up. Low to moderate 2C-B doses were reported by 9 patients (28%), high doses by 17 (53%), and unknown doses by 6 (19%). Poisoning was moderate in the majority of patients in both the low- to moderate-dose and high-dose groups. Frequently reported symptoms included mydriasis, agitation or aggression, hallucinations, confusion, anxiety, hypertension, and tachycardia. The presence of 2C-B was confirmed in 5 patients in urine (n=3) or drug samples (n=4). Conclusion In this study, most 2C-B poisonings resulted in moderate toxicity even at high reported doses up to 192 mg. No severe cases were observed. The clinical course was usually short-lived (up to 24 hours) and typically involved hallucinations in addition to mild somatic effects.

In the search for improved laboratory methods for the diagnosis of ethylene glycol poisoning, the in vivo formation of a glucuronide metabolite of ethylene glycol was hypothesized. Chemically pure standards of the β‐O‐glucuronide of ethylene glycol (EG‐GLUC) and a deuterated analog (d4‐EG‐GLUC) were synthesized. A high‐performance liquid chromatography and tandem mass spectrometry method for determination of EG‐GLUC in serum after ultrafiltration was validated. Inter‐assay precision (%RSD) was 3.9% to 15.1% and inter‐assay %bias was −2.8% to 12.2%. The measuring range was 2–100 μmol/L (0.48–24 mg/L). Specificity testing showed no endogenous amounts in routine clinical samples (n = 40). The method was used to analyze authentic, clinical serum samples (n = 31) from patients intoxicated with ethylene glycol. EG‐GLUC was quantified in 15 of these samples, with a mean concentration of 6.5 μmol/L (1.6 mg/L), ranging from 2.3 to 15.6 μmol/L (0.55 to 3.7 mg/L). In five samples, EG‐GLUC was detected below the limit of quantification (2 μmol/L) and it was below the limit of detection in 11 samples (1 μmol/L). Compared to the millimolar concentrations of ethylene glycol present in blood after intoxications and potentially available for conjugation, the concentrations of EG‐GLUC found in clinical serum samples are very low, but comparable to concentrations of ethyl glucuronide after medium dose ethanol intake. In theory, EG‐GLUC has a potential value as a biomarker for ethylene glycol intake, but the pharmacokinetic properties, in vivo/vitro stability and the biosynthetic pathways of EG‐GLUC must be further studied in a larger number of patients and other biological matrices.

Mercury in dental amalgams : A great concern for clinical toxicology in developing countries?

KARA, ISMAIL HAMDI/0000-0003-2022-1882 WOS: 000394362200017 PubMed: 27495248 Carbon monoxide (CO) is a colourless and odourless gas appearing as a result of incomplete combustion of carbon-containing fuels. Many domestic or occupational poisonings are caused by CO exposure. Malfunctioning heating systems, improperly ventilated motor vehicles, generators, grills, stoves and residential fires may be listed in the common sources of CO exposure. The aim of this study was to emphasize the significance of early diagnosis of CO poisoning with non-invasive measurement of CO levels of the patients with nonspecific symptoms using a pulse oximeter device in the triage. Our study was a cross-sectional study. Patients who presented to the emergency department (ED)due to non-specific symptoms and had a Canadian Triage and Acuity scale level of 4 or 5 were included in the study; 106 (5.9%) of 1788 patients admitted during the study period were diagnosed with CO poisoning. Patients with CO poisoning and the other patients had statistically significant differences in terms of presenting symptoms, namely, headache, dizziness, nausea, and vomiting. More CO poisoning cases were admitted in the fall and winter compared to the spring and summer. The number of CO poisoning victims can be decreased if preventive measures like CO monitoring systems and well-designed ventilation systems are generalized at homes and workplaces. Measurement of carboxyhaemoglobin levels of patients presenting to ED due to non-specific symptoms like headache and dizziness during cold seasons and winter months using a pulse CO-oximeter should be a part of the routine of emergency medicine triage.

This paper reviews high-resolution mass spectrometry (HRMS) approaches using time-of-flight or Orbitrap techniques for research and application in various toxicology fields, particularly in clinical toxicology and forensic toxicology published since 2013 and referenced in PubMed. In the introduction, an overview on applications of HRMS in various toxicology fields is given with reference to current review articles. Papers concerning HRMS in metabolism, screening, and quantification of pharmaceuticals, drugs of abuse, and toxins in human body samples are critically reviewed. Finally, a discussion on advantages as well as limitations and future perspectives of these methods is included.

The field of new psychoactive substances (NPS) is highly dynamic and the situation changes from year to year. Therefore, the current review provides a timely update about the latest developments to help analysts keep the pace with NPS distribution. It covers PubMed-listed studies published between January 2014 and January 2016 dealing with the application of liquid chromatography (LC) coupled low- and high-resolution mass spectrometry (MS) for broad screenings for NPS in clinical (CT) and forensic (FT) toxicology. Latest developments and applications are highlighted and selected papers critically discussed. Comprehensive tables summarizing all discussed articles complete the overview. Finally, an outlook on the future of LC coupled MS in CT and FT is provided and readers will learn why low-resolution mass spectrometry might remain the standard for the next couple of years at least for easy-to-use quantitative screening procedures.

Intravenous lipid emulsions (ILEs) were initially developed to provide parenteral nutrition. In recent years, ILE has emerged as a treatment for poisoning by local anesthetics and various other drugs. The dosing regimen for the clinical toxicology indications differs significantly from those used for parenteral nutrition. The evidence on the efficacy of ILE to reverse acute toxicity of diverse substances consists mainly of case reports and animal experiments. Adverse events to ILE are important to consider when clinicians need to make a risk/benefit analysis for this therapy.Multiple publication databases were searched to identify reports of adverse effects associated with acute ILE administration for either treatment of acute poisoning or parenteral nutrition. Articles were selected based on pre-defined criteria to reflect acute use of ILE. Experimental studies and reports of adverse effects as a complication of long-term therapy exceeding 14 days were excluded.The search identified 789 full-text articles, of which 114 met the study criteria. 27 were animal studies, and 87 were human studies. The adverse effects associated with acute ILE administration included acute kidney injury, cardiac arrest, ventilation perfusion mismatch, acute lung injury, venous thromboembolism, hypersensitivity, fat embolism, fat overload syndrome, pancreatitis, extracorporeal circulation machine circuit obstruction, allergic reaction, and increased susceptibility to infection.The emerging use of ILE administration in clinical toxicology warrants careful attention to its potential adverse effects. The dosing regimen and context of administration leading to the adverse events documented in this review are not generalizable to all clinical toxicology scenarios. Adverse effects seem to be proportional to the rate of infusion as well as total dose received. Further safety studies in humans and reporting of adverse events associated with ILE administration at the doses advocated in current clinical toxicology literature are needed.