Auswahl der wissenschaftlichen Literatur zum Thema „Liquid and gas chromatography coupled with tandem mass spectrometry and high resolution mass spectrometry (UHPLC/GC - MS/MS and UHPLC-HRMS)“

Background: Jamu is commonly known as an Indonesian traditional herbal medicine that contains ingredients or ingredients derived from plants, animals, minerals, galenic, or mixtures of these ingredients that have been hereditary for medicinal use. Some studies reported the presence of medicinal chemicals that are deliberately added to Jamu. Jamuthat containing medicinal chemicals usually had a faster healing effect compared to Jamu that do not contain medicinal chemicals. Jamu added medicinal chemicals cause serious side effects if it is consumed regularly, overdose, and long period consumption with uncontrolled dosage or its interaction with other substances on jamu formulation. Purpose: This review article aims to summarize several methods used to analyze medicinal chemicals contained in jamu. Data source:The author created thisreview article by conducting literature studies. The literature was collected from national and international journals published in the last ten years (2010-2020). The works of literature were collected from trusted online journal sites such as the digital library, Google, Google scholar/Google Cendekia, PubMed, ScienceDirect, NCBI, Researchgate, and other E-resource with the keyword “Jamu”, “medicinal chemicals”, and “analysis of medicinal chemicals”. Conclusion: Jamu products that containing medicinal chemicals are jamu pegal linu, weight loss, stamina enhancer, diabetes, antihypertensive and dietary supplements. The medicinal chemicals used are sodium diclofenac, paracetamol, piroxicam, ibuprofen, dexamethasone, mefenamic acid, phenolphthalein, sibutramine, fenfluramine, sildenafil, tadalafil, thiosildenafil, caffeine, ephedrine, nifedipine, glibenclamide. Herbal Medicine was analyzed by the TLC method (thin layer chromatography), Densitometry-chromatography, thin-layer chromatography-Spectrophotometry, SERS-thin layer chromatography, Spectrophotometry, HPLC (High-Performance Liquid Chromatography), HPLC-ESI-MS/MS (high-performance liquid. chromatography/electrospray ionization tandem mass spectrometry), HPLC-Densitometry (High-Performance Liquid Chromatography-densitometry), UHPLC-Q-ORTIP HERMS (ultra-high-performance liquid chromatography-Quadrupole-orbitrap high-resolution mass spectrometry), UPLC/Q-TOF MS (ultra-performance liquid chromatography (UPLC) coupled with quadrupole-time-of-flight mass spectrometry (Q-TOF MS), Capillary electrophoresis (CE), GC-MS (Gas Chromatography-Mass Spectrometry), LC-MS (Liquid Crhomatogaph Mass) Spectrometry), Prototype Test-Strip, Infrared spectroscopy.

Despite the awareness that work in the sewage treatment plant is associated with biological hazards, they have not been fully recognised so far. The research aims to comprehensively evaluate microbiological and toxicological hazards in the air and settled dust in workstations in a sewage treatment plant. The number of microorganisms in the air and settled dust was determined using the culture method and the diversity was evaluated using high-throughput sequencing. Endotoxin concentration was assessed with GC-MS (gas chromatography-mass spectrometry) while secondary metabolites with LC-MS/MS (liquid chromatography coupled to tandem mass spectrometry). Moreover, cytotoxicity of settled dust against a human lung epithelial lung cell line was determined with the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and UHPLC-Q-ToF-UHRMS (ultra-high-performance liquid chromatography-quadrupole time-of-flight ultrahigh-resolution mass spectrometry) analysis was performed to determine the source of cytotoxicity. The total dust concentration in the sewage treatment plant was low and ranged from 0.030 mg m−3 to 0.044 mg m−3. The highest microbiological contamination was observed in sludge thickening building and screenings storage. Three secondary metabolites were detected in the air and sixteen in the settled dust. They were dominated by compounds typical of lichen and plants and Aspergillus, Penicillium and Fusarium genera mould. The settled dust from the sludge thickening building revealed high cytotoxicity to human lung epithelial cells A-549 (IC50 = 6.98 after 72 h). This effect can be attributed to a biocidal compound—didecyldimethylammonium chloride (DDAC-C10) and seven toxic compounds: 4-hydroxynonenal, carbofuran, cerulenin, diethylphosphate, fenpropimorph, naphthalene and onchidal. The presence of DDAC-C10 and other biocidal substances in the sewage treatment plant environment may bring negative results for biological sewage treatment and the natural environment in the future and contribute to microorganisms’ increasing antibiotics resistance. Therefore, the concentration of antibiotics, pesticides and disinfectants in sewage treatment plant workstations should be monitored.

Bruguiera cylindrica parts are commonly used in Chinese and Indian traditional medicine to treat diarrhea, fever, and many ailments. The present study aims non targeted analysis of key secondary metabolites of B. cylindrica by gas chromatography mass spectrometry (GC-MS) and ultra-high performance liquid chromatography hybrid quadrupole-Exactive-Orbitrap high resolution mass spectrometry (UHPLC-Q-Exactive Orbitrap HRMS). GC-MS and UHPLC-Q-Exactive Orbitrap HRMS were utilized for metabolic profiling of ethyl acetate extract of B. cylindrica leaves. Key metabolites in the extract were identified and predicted based on chemical similarity using online databases such as ChemSpider and mzCloud. Thirty-six compounds belonging to different classes of secondary metabolites viz. flavonoids, fatty acids, fatty acid amides, carboxylic acids, and alkaloids were identified in the extract. Pentacyclic triterpenes like betulin, ursolic acid and a tropine, an alkaloid with potential pharmacological and therapeutic activities such as anticancer properties, neuromuscular blockers and antioxidants, were also identified. This study combined GC-MS and UHPLC-Q-Exactive Orbitrap HRMS with available online database for effective and rapid identification of bioactive metabolites in the ethyl acetate extract of mangrove without individual standard application. This is the first report on the HRMS based secondary metabolic profiling of B. cylindrica, with comprehensive map of its biologically important metabolites.

The consumption of synthetic cannabinoids (SCs) has significantly increased in the last decade and the analysis of SCs and their metabolites in human specimens is gaining interest in clinical and forensic toxicology. A pilot study has been carried out using a combination of an initial last generation gas chromatography-mass spectrometry (GC-MS) screening method for the determination of JWH-122, JWH-210, UR-144) in oral fluid (OF) of consumers and an ultra-high performance liquid chromatography high resolution mass spectrometry (UHPLC-HRMS) confirmatory method for the quantification of the parent compounds and their metabolites in the same biological matrix. OF samples were simply liquid-liquid extracted before injecting in both chromatographic systems. The developed methods have been successfully validated and were linear from limit of quantification (LOQ) to 50 ng/mL OF. Recovery of analytes was always higher than 70% and matrix effect always lower than 15% whereas intra-assay and inter-assay precision and accuracy were always better than 16%. After smoking 1 mg JWH-122 or UR-144 and 3 mg JWH-210, maximum concentration of 4.00–3.14 ng/mL JWH-122, 8.10–7.30 ng/mL JWH-210 ng/mL and 7.40 and 6.81 ng/mL UR-144 were measured by GC-MS and UHPLC-HRMS respectively at 20 min after inhalation. Metabolites of JWH 122 and 210 were quantified in OF by UHPLC-HRMS, while that of UR144 was only detectable in traces. Our results provide for the first time information about disposition of these SCs and their metabolites in consumers OF. Last generation GC-MS has proven useful tool to identify and quantify parent SCs whereas UHPLC-HRMS also confirmed the presence of SCs metabolites in the OF of SCs consumers.

Canine babesiosis is an important tick-borne disease worldwide, caused by parasites of the Babesia genus. Although the disease process primarily affects erythrocytes, it may also have multisystemic consequences. The goal of this study was to explore and characterize the serum metabolome, by identifying potential metabolites and metabolic pathways in dogs naturally infected with Babesia canis using liquid and gas chromatography coupled to mass spectrometry. The study included 12 dogs naturally infected with B. canis and 12 healthy dogs. By combining three different analytical platforms using untargeted and targeted approaches, 295 metabolites were detected. The untargeted ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) metabolomics approach identified 64 metabolites, the targeted UHPLC-MS/MS metabolomics approach identified 205 metabolites, and the GC-MS metabolomics approach identified 26 metabolites. Biological functions of differentially abundant metabolites indicate the involvement of various pathways in canine babesiosis including the following: glutathione metabolism; alanine, aspartate, and glutamate metabolism; glyoxylate and dicarboxylate metabolism; cysteine and methionine metabolism; and phenylalanine, tyrosine, and tryptophan biosynthesis. This study confirmed that host–pathogen interactions could be studied by metabolomics to assess chemical changes in the host, such that the differences in serum metabolome between dogs with B. canis infection and healthy dogs can be detected with liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) methods. Our study provides novel insight into pathophysiological mechanisms of B. canis infection.

The use of the new psychoactive substances is continuously growing and the implementation of accurate and sensible analysis in biological matrices of users is relevant and fundamental for clinical and forensic purposes. Two different analytical technologies, high-sensitivity gas chromatography-mass spectrometry (GC-MS) and ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) were used for a screening analysis of classic drugs and new psychoactive substances and their metabolites in urine of formed heroin addicts under methadone maintenance therapy. Sample preparation involved a liquid-liquid extraction. The UHPLC-HRMS method included Accucore™ phenyl Hexyl (100 × 2.1 mm, 2.6 μm, Thermo, USA) column with a gradient mobile phase consisting of mobile phase A (ammonium formate 2 mM in water, 0.1% formic acid) and mobile phase B (ammonium formate 2 mM in methanol/acetonitrile 50:50 (v/v), 0.1% formic acid) and a full-scan data-dependent MS2 (ddMS2) mode for substances identification (mass range 100–1000 m/z). The GC-MS method employed an ultra-Inert Intuvo GC column (HP-5MS UI, 30 m, 250 µm i.d, film thickness 0.25 µm; Agilent Technologies, Santa Clara, CA, USA) and electron-impact (EI) mass spectra were recorded in total ion monitoring mode (scan range 40–550 m/z). Urine samples from 296 patients with a history of opioid use disorder were examined. Around 80 different psychoactive substances and/or metabolites were identified, being methadone and metabolites the most prevalent ones. The possibility to screen for a huge number of psychotropic substances can be useful in suspected drug related fatalities or acute intoxication/exposure occurring in emergency departments and drug addiction services.

This study aimed to investigate the detection of morphine in fingernails from forensic autopsies using immunohistochemistry (IHC), with confirmation by ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-HRMS). A primary antibody specific to morphine and a secondary antibody conjugated to horseradish peroxidase (HRP) was used. IHC on specimens of Subjects A and B (both drug addicts) resulted in the detection of morphine on a cell layer of the nail plate matrix. UHPLC-HRMS and GC-MS analysis showed that Subject A had a morphine concentration of 0.35 ng/mg in the fingernail and 472 ng/mL in the blood, while Subject B reached 1.23 ng/mg in the fingernail and 360 ng/ml in the blood. Most of those matrices were positive for codeine, methadone, EDDP, and 6-MAM. The use of IHC in Subject C (a former addict) showed no positivity for morphine in the fingernail, while the UHPLC-HRMS analysis confirmed its absence in the fingernail and blood. Additionally, an analysis of the scalp or pubic hair of the subjects was carried out using UHPLC-HRMS. The results suggest that IHC can be used to establish the site of accumulation of morphine in the nail matrix; for postmortem diagnosis; and that basic substances can be detected by UHPLC-HRMS. There are no previous studies on the use of IHC as a technique for forensic purposes in unconventional matrices, such as nails.

Background and Objectives: The use of synthetic cannabinoids has increased around the world. As a result, the implementation of accurate analysis in human biological matrices is relevant and fundamental. Two different analytical technologies, ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) and high-sensitivity gas chromatography-mass spectrometry (GC-MS) were used for the determination of three synthetic cannabinoids JWH-122, JWH 210, UR-144 and their metabolites in urine of consumers. Materials and Methods: Sample preparation included an initial hydrolysis with β-glucuronidase and liquid-liquid extraction. The UHPLC-HRMS method included a Kinetex 2.6 u Biphenyl 100A (100 × 2.1 mm, 2.6 μm) (Phenomenex, Italy) column with a gradient mobile phase consisting of mobile phase A (ammonium formate 2mM in water, 0.1% formic acid) and mobile phase B (ammonium formate 2mM in methanol/acetonitrile 50:50 (v/v), 0.1% formic acid) and a full-scan data-dependent MS2 (ddMS2) mode was used (mass range 100–1000 m/z). The GC-MS method employed an ultra-Inert Intuvo GC column (HP-5MS UI, 30 m × 250 µm i.d, film thickness 0.25 µm; Agilent Technologies, Santa Clara, CA, USA) and electron-impact (EI) mass spectra were recorded in total ion monitoring mode (scan range 40–550 m/z). Results: Both methods have been successfully used for screening of parent synthetic cannabinoids and their metabolites in urine samples of consumers. Conclusions: The screening method applied JWH-122, JWH-210, UR-144 and their metabolites in urine of consumers can be applied to other compounds of the JWH family.

Ultra-high performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS) is a powerful and essential technique for metabolite annotation in untargeted metabolomic applications. The aim of this study was to evaluate the performance of diverse tandem MS (MS/MS) acquisition modes, i.e., all ion fragmentation (AIF) and data-dependent analysis (DDA), with and without ion mobility spectrometry (IM), to annotate metabolites in human plasma. The influence of the LC separation was also evaluated by comparing the performance of MS/MS acquisition in combination with three complementary chromatographic separation modes: reversed-phase chromatography (RPLC) and hydrophilic interaction chromatography (HILIC) with either an amide (aHILIC) or a zwitterionic (zHILIC) stationary phase. RPLC conditions were first chosen to investigate all the tandem MS modes, and we found out that DDA did not provide a significant additional amount of chemical coverage and that cleaner MS/MS spectra can be obtained by performing AIF acquisitions in combination with IM. Finally, we were able to annotate 338 unique metabolites and demonstrated that zHILIC was a powerful complementary approach to both the RPLC and aHILIC chromatographic modes. Moreover, a better analytical throughput was reached for an almost negligible loss of metabolite coverage when IM-AIF and AIF using ramped instead of fixed collision energies were used.

The influence of ozone (O3) gas on reducing the contamination with Fusarium mycotoxins in malting wheat grains was investigated. Ultra-high performance liquid chromatography coupled to triple quadrupole tandem mass spectrometry (UHPLC-QqQ-MS/MS) and Orbitrap high resolution mass spectrometry (UHPLC-Orbitrap-HRMS) were used to determine mycotoxins in wheat grains before and 40 to 130 min after the exposure to 20 mg/l O3. Pearson’s analysis (R2=0.96-0.98) showed a good correlation between the performance efficiency of both mass spectrometry quantification techniques. The concentrations of determined mycotoxins (zearalenone (ZEA): 19.5-459 µg/kg, deoxynivalenol (DON): 3,370-4,620 µg/kg, T-2 toxin: 19.5-35.4 µg/kg, and HT-2 toxin: 258-819 µg/kg) decreased notably, depending on the duration of contact with ozone. A notable elimination of ZEA, HT-2, and T-2 in wheat grain was observed: the content of these compounds was reduced on average by 58.6, 64.6, and 62%, respectively, already after 40 min of ozonation. The effect was less pronounced in the case of DON, for which the average degradation rate reached the maximum of only 25% after 130 min exposure. We conclude that ozonation for up to 130 min was effective for reducing the content of most mycotoxins determined in this study, except for DON, in contaminated grains to concentrations below the acceptable maximum levels in wheat in accordance to the EU regulations.

L'utilisation des médicaments antidiabétiques, malgré leurs fins thérapeutiques, n'est pas dénuée de risques. Le plus grand risque lié à l'utilisation de ces médicaments est l'hypoglycémie, qui peut être fatale en cas d'utilisation inappropriée. L'utilisation détournée est en fait assez bien connue à des fins criminelles de suicide et de meurtre, comme substances dopantes dans le milieu sportif (dans le cas de l'insuline) et dans le cadre des hypoglycémies factices (syndrome de Münchhausen). Dans le cadre de ma thèse, je me suis intéressé à 5 familles d'antidiabétiques oraux (sulfamides hypoglycémiants, glinides, gliptines, biguanides et gliflozines) et à l'insuline. L'objectif principal était de développer des méthodes analytiques pour l'identification et la quantification de ces substances dans le sang et autres fluides biologiques et d'apporter un intérêt à la recherche de ces substances dans les cheveux afin de fournir des critères d'interprétation pour mieux expliquer les concentrations retrouvées dans les cheveux en raison du manque de données dans la littérature. La première partie de ce travail a été consacrée au développement de méthodes analytiques pour détecter les antidiabétiques oraux dans le sang et les cheveux par chromatographie en phase gazeuse couplée à la spectrométrie de masse en tandem en ce qui concerne la metformine et à l’aide de la chromatographie liquide couplée à la spectrométrie de masse en tandem pour les autres quatre familles d’antidiabétiques oraux. Après avoir développé des méthodes analytiques pour la recherche d'antidiabétiques oraux, mon travail s'est orienté vers le développement d'une méthode d'identification de l'insuline dans la matrice sanguine postmortem sur un système de chromatographie liquide couplé à la spectrométrie de masse à haute résolution (Q-TOF). Aujourd'hui, les bibliothèques de MS contiennent six antidiabétiques appartenant à la famille des sulfamides comme agents hypoglycémiants, un biguanide (metformine), deux glinides, cinq gliptines et trois gliflozines . En outre, elles comptent désormais aussi les spectres de l'insuline humaine et de cinq de ses analogues synthétiques. Ces méthodes ont été appliquées à la fois dans des contextes cliniques pour l'ajustement de la posologie et aux cas de surdosage provenant de la réanimation et des urgences, et dans des cas médico-légaux impliquant principalement des suicides et des surdosages dus à une mauvaise utilisation de ces médicaments. Ces travaux ont donné lieu à 7 publications internationales et 3 publications nationales
The use of anti-diabetic drugs, despite their therapeutic purposes, is not risk-free. The greatest risk associated with the use of these drugs is hypoglycaemia, which can be fatal if used inappropriately. Misuse is actually quite well known for criminal purposes of suicide and murder, for doping purposes in sports (in the case of insulin) and in the context of factitious hypoglycaemia (Munchausen syndrome). In my thesis, I was interested in 5 families of oral antidiabetic drugs (hypoglycaemic sulphonamides, glinides, gliptins, biguanides and gliflozins) and in insulin. The main objective was to develop analytical methods for the identification and quantification of these substances in blood and other biological fluids and to provide an interest in the research of these substances in hair in order to provide interpretation criteria to better explain the concentrations found in hair due to the lack of data in the literature. The first part of this work was devoted to the development of analytical methods to detect oral antidiabetic drugs in blood and hair by gas chromatography-tandem mass spectrometry for metformin and by liquid chromatography-tandem mass spectrometry for the other four families of oral antidiabetic drugs. After developing analytical methods for the investigation of oral antidiabetics,my work turned to the development of a method for the identification of insulin in the postmortem blood matrix on a liquid chromatography-high resolution mass spectrometry (Q-TOF) system. Today, the MS libraries contain six antidiabetic drugs belonging to the sulphonamide family as hypoglycaemicagents, one biguanide (metformin), two glinides, five gliptins and three gliflozins. In addition, they now also include the spectra of human insulin and five of its synthetic analogues. These methods have been applied both in clinical settings for dose adjustment and overdose cases from the intensive care unit and emergency room, and in forensic cases involving mainly suicides and overdoses due to incorrect use of these drugs. This work has led to 7 international and 3 national publications

Extra virgin olive oil (EVOO) is a high value commodity that might be subject of various fraudulent practices. One of them, addition of lower grade, soft-deodorized olive oil to EVOO has recently become of concern, as such adulterant detection is not an easy task. In this study, aqueous methanolic extracts of a unique set of authentic EVOOs, soft-deodorized oils and their admixtures obtained within the OLEUM EU project (http://www.oleumproject.eu/) were investigated. Using ultra-high performance liquid chromatography coupled to hybrid quadrupole time-of-flight high-resolution tandem mass spectrometry (UHPLC-QTOF-HRMS/MS) for metabolomic fingerprinting, followed by  multi-dimensional chemometric evaluation, ´marker ions´ were recognized. Some molecules identified, whose etiology must be investigated, were: the methyl ester of hydroxy octadecenoic acid and a ester derivative of oleic acid. As far as these markers can be confirmed as diagnostic, detection of soft-deodorized olive oil addition can be enabled through a simpler and highly sensitive target analysis employing high performance liquid chromatography coupled to triple quadrupole tandem mass spectrometry (HPLC-QqQ-MS/MS).