scholarly journals Towards Extending the Detection Window of Gamma-Hydroxybutyric Acid—An Untargeted Metabolomics Study in Serum and Urine Following Controlled Administration in Healthy Men

Metabolites ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 166
Author(s):  
Andrea E. Steuer ◽  
Justine Raeber ◽  
Fabio Simbuerger ◽  
Dario A. Dornbierer ◽  
Oliver G. Bosch ◽  
...  
Keyword(s):  
Drugs Of Abuse ◽  
Forensic Toxicology ◽  
Reversed Phase ◽  
Mixed Effect ◽  
Healthy Men ◽  
Metabolic Substrates ◽  
Gamma Hydroxybutyrate ◽  
Metabolomics Study ◽  
Detection Window ◽  
Negative Electrospray Ionization

In forensic toxicology, gamma-hydroxybutyrate (GHB) still represents one of the most challenging drugs of abuse in terms of analytical detection and interpretation. Given its rapid elimination, the detection window of GHB in common matrices is short (maximum 12 h in urine). Additionally, the differentiation from naturally occurring endogenous GHB, is challenging. Thus, novel biomarkers to extend the detection window of GHB are urgently needed. The present study aimed at searching new potential biomarkers of GHB use by means of mass spectrometry (MS) metabolomic profiling in serum (up to 16.5 h) and urine samples (up to 8 h after intake) collected during a placebo-controlled crossover study in healthy men. MS data acquired by different analytical methods (reversed phase and hydrophilic interaction liquid chromatography; positive and negative electrospray ionization each) were filtered for significantly changed features applying univariate and mixed-effect model statistics. Complementary to a former study, conjugates of GHB with glycine, glutamate, taurine, carnitine and pentose (ribose) were identified in urine, with particularly GHB-pentose being promising for longer detection. None of the conjugates were detectable in serum. Therein, mainly energy metabolic substrates were identified, which may be useful for more detailed interpretation of underlying pathways but are too unspecific as biomarkers.

Simultaneous and Sensitive Determination of Amphetamine, Codeine and Morphine in Exhaled Breath Condensate, Using Capillary Electrophoresis Coupled with On-line and Off-line Enhancing Methods

2020 ◽  
Vol 16 (7) ◽  
pp. 872-879
Author(s):  
Samin Hamidi
Keyword(s):  
Drugs Of Abuse ◽  
Exhaled Breath Condensate ◽  
Direct Injection ◽  
Forensic Toxicology ◽  
Analytical Signal ◽  
Exhaled Breath ◽  
Concentration Method ◽  
Validation Parameters ◽  
Breath Condensate

Background: Abuse of drugs is associated with several medical, forensic, toxicology and social challenges. “Drugs of abuse” testing is therefore an important issue. Objective: We propose a simple CE-based method for the quantification of amphetamine, codeine and morphine after direct injection of Exhaled Breath Condensate (EBC) by the aid of simple stacking mode and an off-line pre-concentration method. Methods: Using graphene oxide adsorbents, amphetamine, codeine and morphine were extracted from EBC in order to eliminate the proteins and other interferences. In addition to off-line method, an online stacking mode was applied to improve the analytical signal obtained from the instrument. Results: The validation parameters were experimented on the developed method based on the FDA guideline over concentration ranges of 12.5-100, 30-500 and 10-1250 ng/mL associated with amphetamine, codeine and morphine, respectively. Small volumes (around 100 μL) of EBC were collected using a lab-made setup and successfully analyzed using the proposed method where precisions and accuracies (within day and between days) were in accordance with the guideline (recommended less than 15 % for biological samples). The recovery tests were used to evaluate the matrix effect and data (94 to 105 %) showed that the proposed method can be applied in different EBC matrix samplings of subjects. Conclusion: The proposed method is superior for simultaneous determination of amphetamine, codeine and morphine over chromatographic analyses because it is fast and consumes fewer chemicals, with no derivatization step.

scholarly journals Development and Validation of a LC–MS/MS-Based Assay for Quantification of Free and Total Omega 3 and 6 Fatty Acids from Human Plasma

Molecules ◽  
2019 ◽  
Vol 24 (2) ◽  
pp. 360 ◽  
Author(s):  
Vlad Serafim ◽  
Diana-Andreea Tiugan ◽  
Nicoleta Andreescu ◽  
Alexandra Mihailescu ◽  
Corina Paul ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Human Plasma ◽  
High Performance ◽  
Multiple Reaction Monitoring ◽  
Reversed Phase ◽  
Omega 3 ◽  
Mass Detection ◽  
Liquid Chromatography Tandem Mass ◽  
Negative Electrospray Ionization ◽  
Nanomolar Range

Few high-performance liquid chromatography–tandem mass spectrometry (LC-MS/MS) methods have been developed for the full quantitation of fatty acids from human plasma without derivatization. Therefore, we propose a method that requires fewer sample preparation steps, which can be used for the quantitation of several polyunsaturated fatty acids in human plasma. The method offers rapid, accurate, sensitive, and simultaneous quantification of omega 3 (α-linolenic, eicosapentaenoic, and docosahexaenoic acids) and omega 6 fatty acids (arachidonic and linoleic acids) using high-performance LC-MS/MS. The selected fatty acids were analysed in lipid extracts from both free and total forms. Chromatographic separation was achieved using a reversed phase C18 column with isocratic flow using ammonium acetate for improving negative electrospray ionization (ESI) response. Mass detection was performed in multiple reaction monitoring (MRM) mode, and deuterated internal standards were used for each target compound. The limits of quantification were situated in the low nanomolar range, excepting linoleic acid, for which the limit was in the high nanomolar range. The method was validated according to the U.S. Department of Health and Human Services guidelines, and offers a fast, sensitive, and reliable quantification of selected omega 3 and 6 fatty acids in human plasma.

Hypothesis on interferences in kinetic interaction of microparticles in solution (KIMS) technology

2006 ◽  
Vol 44 (7) ◽  
Author(s):  
Nadia De Giovanni ◽  
Nadia Fucci
Keyword(s):  
Mass Spectrometry ◽  
Air Force ◽  
High Frequency ◽  
Drugs Of Abuse ◽  
Forensic Toxicology ◽  
Pharmacological Therapy ◽  
Gas Chromatography Mass Spectrometry ◽  
Drug Test ◽  
Kinetic Interaction ◽  
Positive Results

AbstractThe present paper describes an evaluation of the interferences found with an immunochemical drug test performed during a workplace control. During the period 1993–2003 more than 200,000 urine samples from workers were examined by the Italian Air Force. Samples were screened for drugs of abuse (opiates, cocaine, cannabinoids, amphetamines, methadone) using an immunochemical technique (Roche, kinetic interaction of microparticles in solution, KIMS). A total of 520 positive samples were sent to the Forensic Toxicology Laboratory for confirmation by gas chromatography/mass spectrometry (GC/MS). Approximately 39% of these were found to be true positives. For the remaining samples, pharmacological therapy in subjects was estimated to evaluate possible interferences due to medicine intake. Our study showed a high frequency of false-positive results with this immunochemical technique, mainly for the cannabinoid and amphetamine groups. Recurrent references to some medicines during subject anamnesis were noted.Clin Chem Lab Med 2006;44;894–7.

scholarly journals Development and Validation of an LC-MS/MS Based Method for the Determination of Deoxynivalenol and Its Modified Forms in Maize

Toxins ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 600
Author(s):  
Iris Fiby ◽  
Marta Magdalena Sopel ◽  
Herbert Michlmayr ◽  
Gerhard Adam ◽  
Franz Berthiller
Keyword(s):  
Matrix Effects ◽  
Internal Standard ◽  
Reversed Phase ◽  
Selected Reaction Monitoring ◽  
Stable Isotope Dilution ◽  
Liquid Chromatography Tandem Mass ◽  
Cereal Samples ◽  
Negative Electrospray Ionization ◽  
Development And Validation ◽  
Modified Forms

The Fusarium mycotoxin deoxynivalenol (DON) is a common contaminant of cereals and is often co-occurring with its modified forms DON-3-glucoside (D3G), 3-acetyl-DON (3ADON) or 15-acetyl-DON (15ADON). A stable-isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS) based method for their determination in cereals was developed and validated for maize. Therefore, 13C-labelled D3G was enzymatically produced using 13C-DON and [13C6Glc]-sucrose and used as an internal standard (IS) for D3G, while uniformly 13C labelled IS was used for the other mycotoxins. Baseline separation was achieved for the critical peak pair DON/D3G, while 3ADON/15ADON could not be fully baseline separated after testing various reversed phase, fluorinated phase and chiral LC columns. After grinding, weighing and extracting the cereal samples, the raw extract was centrifuged and a mixture of the four 13C-labelled ISs was added directly in a microinsert vial. The subsequent analytical run took 7 min, followed by negative electrospray ionization and selected reaction monitoring on a triple quadrupole MS. Maize was used as a complex cereal model matrix for validation. The use of the IS corrected the occurring matrix effects efficiently from 76 to 98% for D3G, from 86 to 103% for DON, from 68 to 100% for 15ADON and from 63 to 96% for 3ADON.

scholarly journals Determination of Chlorinated Acid Herbicides in Vegetation and Soil by Liquid Chromatography/Electrospray-Tandem Mass Spectrometry

2007 ◽  
Vol 90 (5) ◽  
pp. 1402-1410 ◽  
Author(s):  
Angela Schaner ◽  
Jaclyn Konecny ◽  
Laura Luckey ◽  
Heidi Hickes
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Tandem Mass Spectrometry ◽  
Solid Phase ◽  
Reversed Phase ◽  
Basic Solution ◽  
Tandem Mass ◽  
Solid Phase Extraction Cartridge ◽  
Negative Electrospray Ionization ◽  
Acid Herbicides

Abstract The method presented uses reversed-phase liquid chromatography with negative electrospray ionization and tandem mass spectrometry to analyze 9 chlorinated acid herbicides in soil and vegetation matrixes: clopyralid, dicamba, MCPP, MCPA, 2,4-DP, 2,4-D, triclopyr, 2,4-DB, and picloram. A 20 g portion is extracted with a basic solution and an aliquot acidified and micropartitioned with 3 mL chloroform. Vegetation samples are subjected to an additional cleanup with a mixed-mode anion exchange solid-phase extraction cartridge. Two precursor product ion transitions per analyte are measured and evaluated to provide the maximum degree of confidence in results. Average recoveries for 3 different soil types tested ranged from 72 to 107 for all compounds with the exception of 2,4-DB at 5699. Average recoveries for the 3 different vegetation types studied were lower and ranged from 53 to 80 for all compounds.

scholarly journals Potential Surrogate Markers for Gamma-Hydroxybutyrate Administration May Extend the Detection Window from 12 to 48 Hours

2007 ◽  
Vol 31 (1) ◽  
pp. 15-22 ◽  
Author(s):  
Scott J. Larson ◽  
Elizabeth A. Putnam ◽  
Corbin M. Schwanke ◽  
Mark A. Pershouse
Keyword(s):  
Surrogate Markers ◽  
Gamma Hydroxybutyrate ◽  
Detection Window

scholarly journals New Advances in Toxicological Forensic Analysis Using Mass Spectrometry Techniques

2018 ◽  
Vol 2018 ◽  
pp. 1-17 ◽  
Author(s):  
Noroska Gabriela Salazar Mogollón ◽  
Cristian Daniel Quiroz-Moreno ◽  
Paloma Santana Prata ◽  
Jose Rafael de Almeida ◽  
Amanda Sofía Cevallos ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Drugs Of Abuse ◽  
Biological Fluids ◽  
Forensic Toxicology ◽  
Forensic Analysis ◽  
New Methodologies ◽  
Identification And Quantification

This article reviews mass spectrometry methods in forensic toxicology for the identification and quantification of drugs of abuse in biological fluids, tissues, and synthetic samples, focusing on the methodologies most commonly used; it also discusses new methodologies in screening and target forensic analyses, as well as the evolution of instrumentation in mass spectrometry.

scholarly journals Comparison of Three Untargeted Data Processing Workflows for Evaluating LC-HRMS Metabolomics Data

Metabolites ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 378 ◽  
Author(s):  
Selina Hemmer ◽  
Sascha K. Manier ◽  
Svenja Fischmann ◽  
Folker Westphal ◽  
Lea Wagmann ◽  
...  
Keyword(s):  
Data Processing ◽  
Open Source ◽  
High Resolution Mass Spectrometry ◽  
Liver Microsomes ◽  
Reversed Phase ◽  
Ease Of Use ◽  
Untargeted Metabolomics ◽  
Metabolomics Data ◽  
Metabolomics Study ◽  
High Flexibility

The evaluation of liquid chromatography high-resolution mass spectrometry (LC-HRMS) raw data is a crucial step in untargeted metabolomics studies to minimize false positive findings. A variety of commercial or open source software solutions are available for such data processing. This study aims to compare three different data processing workflows (Compound Discoverer 3.1, XCMS Online combined with MetaboAnalyst 4.0, and a manually programmed tool using R) to investigate LC-HRMS data of an untargeted metabolomics study. Simple but highly standardized datasets for evaluation were prepared by incubating pHLM (pooled human liver microsomes) with the synthetic cannabinoid A-CHMINACA. LC-HRMS analysis was performed using normal- and reversed-phase chromatography followed by full scan MS in positive and negative mode. MS/MS spectra of significant features were subsequently recorded in a separate run. The outcome of each workflow was evaluated by its number of significant features, peak shape quality, and the results of the multivariate statistics. Compound Discoverer as an all-in-one solution is characterized by its ease of use and seems, therefore, suitable for simple and small metabolomic studies. The two open source solutions allowed extensive customization but particularly, in the case of R, made advanced programming skills necessary. Nevertheless, both provided high flexibility and may be suitable for more complex studies and questions.

scholarly journals A comparison between two different dried blood substrates in determination of psychoactive substances in postmortem samples

2021 ◽  
Author(s):  
Matteo Moretti ◽  
Alessandro Manfredi ◽  
Francesca Freni ◽  
Carlo Previderé ◽  
Antonio Marco Maria Osculati ◽  
...  
Keyword(s):  
Drugs Of Abuse ◽  
Forensic Toxicology ◽  
Dried Blood Spots ◽  
Psychoactive Substances ◽  
Extraction Solvent ◽  
Quantitative Correlation ◽  
Fta Cards ◽  
Postmortem Blood ◽  
Quantitative Results

Abstract Purpose Whatman™ 903 cards represent a valid type of support for collection, storage, and analysis of dried blood spots (DBS). Whatman™ FTA (Flinders Technology Associates) are a type of cards soaked in chemicals that cause denaturation of proteins, while preserving DNA and ensuring the safe handling of DBS; to date, these cards are still rarely employed in forensic toxicology. The aim of this study was to analyze several psychoactive substances on not-dried blood on the two different cards and to compare the qualitative and quantitative results. Methods Twenty cardiac postmortem blood samples were collected and deposed on Whatman™ 903 and Whatman™ FTA cards. Spots and not-dried blood were analyzed following our validated and previously published liquid chromatography–mass spectrometry methods. Results We were able to identify: eight drugs of abuse and their metabolites (15 cases), five benzodiazepines and their metabolites (3 cases), six antidepressants (6 cases) and two antipsychotics (3 cases). We observed a perfect qualitative correspondence and a general good quantitative correlation between data obtained from not-dried blood and the two different DBS cards, except for alprazolam, diazepam, desmethyldiazepam, fluoxetine and sertraline, that showed a lower concentration on FTA. Additional experiments suggest that the chemicals, adsorbed on FTA, are not the cause of the loss of signal observed for the substances previously mentioned and that methanol should be preferred as extraction solvent. Conclusions This study proved that FTA cards are a good and a hazard-free alternative sample storage method for analysis of several psychoactive substances in postmortem blood.

scholarly journals Pharmacogenetics and Forensic Toxicology: A New Step towards a Multidisciplinary Approach

Toxics ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 292
Author(s):  
Nunzio Di Nunno ◽  
Massimiliano Esposito ◽  
Antonina Argo ◽  
Monica Salerno ◽  
Francesco Sessa
Keyword(s):  
Drugs Of Abuse ◽  
Case Reports ◽  
Forensic Toxicology ◽  
Good Health ◽  
Post Mortem ◽  
Pharmacogenetic Study ◽  
Forensic Practice ◽  
Toxicological Data ◽  
The Individual ◽  
Overdose Deaths

Pharmacogenetics analyzes the individual behavior of DNA genes after the administration of a drug. Pharmacogenetic research has been implemented in recent years thanks to the improvement in genome sequencing techniques and molecular genetics. In addition to medical purposes, pharmacogenetics can constitute an important tool for clarifying the interpretation of toxicological data in post-mortem examinations, sometimes crucial for determining the cause and modality of death. The purpose of this systematic literature review is not only to raise awareness among the forensic community concerning pharmacogenetics, but also to provide a workflow for forensic toxicologists to follow in cases of unknown causes of death related to drug use/abuse. The scientific community is called on to work hard in order to supply evidence in forensic practice, demonstrating that this investigation could become an essential tool both in civil and forensic contexts. The following keywords were used for the search engine: (pharmacogenetics) AND (forensic toxicology); (pharmacogenetics) AND (post-mortem); (pharmacogenetics) AND (forensic science); and (pharmacogenetics) AND (autopsy). A total of 125 articles were collected. Of these, 29 articles were included in this systematic review. A total of 75% of the included studies were original articles (n = 21) and 25% were case reports (n = 7). A total of 78% (n = 22) of the studies involved deceased people for whom a complete autopsy was performed, while 22% (n = 6) involved people in good health who were given a drug with a subsequent pharmacogenetic study. The most studied drugs were opioids (codeine, morphine, and methadone), followed by antidepressants (tricyclic antidepressants and venlafaxine). Furthermore, all studies highlighted the importance of a pharmacogenetics study in drug-related deaths, especially in cases of non-overdose of drugs of abuse. This study highlights the importance of forensic pharmacogenetics, a field of toxicology still not fully understood, which is of great help in cases of sudden death, deaths from overdose, deaths after the administration of a drug, and also in cases of complaint of medical malpractice.

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