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BACKGROUND: Liquid chromatography-high-resolution mass spectrometry (LC-HR-MS) has emerged as a powerful analytical technology for compound screening in clinical toxicology. To evaluate the potential of LC-HR-MS3 in detecting toxic natural products, a spectral library of 85 natural products (79 alkaloids) that contains both MS2 and MS3 mass spectra was constructed and used to identify the natural products. Samples were analyzed using an LC-HR-MS3 method and the generated data were matched to the spectral library to identify the natural products. METHODS: To test the performance of the LC-HR-MS3 method in different sample matrices, the 85 natural product standards were divided into three groups to separate structural isomers and avoid ion suppression effects caused by co-elution of multiple analytes. The grouped analytes were spiked into drug-free serum and drug-free urine to produce contrived clinical samples. RESULTS: The compound identification results of the 85 natural products in urine and serum samples were obtained. The match scores using both MS2 and MS3 mass spectra and those using only MS2 mass spectra were compared at 10 different analyte concentrations. The two types of data analysis provided identical identification results for the majority of the analytes (96% in serum, 92% in urine), whereas, for the remaining analytes, the MS2-MS3 tree data analysis had better performance in identifying them at lower concentrations. CONCLUSION: This study shows that in comparison to LC-HR-MS (MS2), LC-HR-MS3 can increase the performance in identification of a small group of the toxic natural products tested in serum and urine specimens.

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.

The constant emergence of New Psychoactive Substances is a challenge to clinical and forensic toxicologists that need to constantly update analytical techniques to detecting 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 GC-MS. The method involves an Ultrasound-Assisted Dispersive Liquid-Liquid Microextraction which implies a rapid procedure, giving excellent extraction efficiencies with minimal use of toxic solvents. This is followed by silylation and analysis with GC-MS. 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), selectivity and linearity (in the range 5 - 200 ng/mL). The developed assay is highly applicable to laboratories with limited instrumental availability, thanks to the use of efficient and low-cost sample preparation and instrumental equipment. The latter may contribute to enhance the detection of NPS in clinical and forensic toxicology laboratories.

The phenomenon of Drug-Facilitated Sexual Assaults (DFSA), has dramatically raised in the past decades, also due to the high number of drugs that can potentially be used. Analytical methods able to detect a large number of drugs with high sensitivity are sought for the diagnosis of DFC. The aim of the present study was the development of an analytical protocol for the identification of a wide number of possible incapacitating substance in biological specimens for its application to alleged victims of DFC. The procedure involves the combination of ten analytical methods, performed by LC-MS/MS, GC–MS, GC-FID. The procedure allows the screening of about 200 drugs/metabolites in urine, blood and hair. The protocol is generally applied to urine samples. Hair analysis is performed in cases where more than 48 h elapsed from the suspected administration; a blood sample is analysed only when less than 12 h elapsed and urine is positive for one or more substance. For its preliminary evaluation, the protocol was applied to analyse biological samples collected on 120 victims of alleged DFSA. Ethanol and/or its metabolite ethylglucuronide was detected in 66% of cases; benzodiazepines and analogues (zolpidem) in 18%; other substances detected were cocaine (in 15 cases), cannabis (in 10 cases) MDMA (8 cases), antipsychotics, antihystaminics, antidepressants, antiepileptics and opiates. GHB was detected at a concentration greater than 10 µg/ml in urine only in one case. The results demonstrate the suitability of the protocol to detect substances potentially used to commit or to facilitate a DFC.

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.

A liquid chromatography–high resolution mass spectrometry (LC-HRMS) method for the simultaneous screening in hair samples of drugs of abuse and medicaments was developed. Target analytes screened using a single extraction and analytical run were opiates, cocaine, amphetamines and amphetamine-like substances, ketamine and analogues, cannabinoids, both natural and synthetic, cathinones, piperazines, ephedrines and others new psychoactive substances not pertaining to these classes; pharmaceutical drugs such as antipsychotics, antiepileptics, antidepressants, benzodiazepines and analogues, anorectics, stimulants, drugs for the erectile dysfunction. The multiresidual method involved methanolic incubation of 30 mg of decontaminated hair and analysis of the extract in HPLC using a C18 column. The mass detector, a benchtop Orbitrap Exactive, with nominal resolving power of 100,000, operated in full scan mode in positive ESI. Analytes were identified by exact mass, correspondence of isotopic cluster and retention times using a home-made database. The database contained the protonated exact masses of each monoisotopic compound, the retention time and the molecular formula of each studied analyte. At the moment the database contains 177 analytes. The screening method was validated for selectivity, limit of detection (LOD), matrix effect and carryover. The limits of detection obtained varied from 2 to 30 pg/mg, and the matrix effect was negligible. This method was then applied to three hundred authentic samples, resulting in the identification of various drugs of abuse and therapeutic drugs. The analyte identity was subsequently confirmed by in-source fragmentation. Thanks to the scan acquisition, this method also enables retrospective re-analysis of the acquired datafile in case a further analyte needs to be screened.

現在流通している医薬品や化学薬品の数は膨大であり,これらを原因とする急性 中毒の診断と治療は時に困難である.救急科専門医は病歴や様々な身体所見,薬毒物スクリー ニングなどを駆使して総合的にその診断を行っている.また近年,数多くの疾患に対する治療 のガイドラインが発表されているが,急性中毒の治療についてもその指針が発表されている. この中では胃洗浄や強制利尿など慣例的に行われてきた治療の多くが見直されている.