Article
Medicine, Research & Experimental
Ni Luo, Ming Sun, Xuhua Han, Linling Li, Lei Wang, Zeneng Cheng
Summary: Mefunidone (MFD), a derivative of pirfenidone, showed promising anti-fibrosis and anti-inflammatory activity in preclinical evaluations. The metabolization of MFD mainly occurs through oxidation, N-demethylation, and hydroxylation pathways. Importantly, MFD did not induce or inhibit metabolic enzymes in preclinical investigations, supporting further clinical research on MFD.
Article
Biochemical Research Methods
Robin Sunsong, Ting Du, Imoh Etim, Yun Zhang, Dong Liang, Song Gao
Summary: The study successfully developed a sensitive LC-MS-MS method to quantify polydatin and its metabolite, resveratrol, for pharmacokinetic study and to determine polydatin hydrolysis by microflora. The method showed good linearity, reproducibility, and stability of analytes in plasma, as well as efficient extraction recovery rates. The metabolic and PK studies revealed rapid hydrolysis of polydatin and exposure of both polydatin and resveratrol in plasma and tissues.
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Peng-fei Tang, Su-su Bao, Nan-yong Gao, Chuan-feng Shao, Wei-fei Xie, Xue-meng Wu, Le-ping Zhao, Zhong-xiang Xiao
Summary: This study established and validated a fast, accurate, stable, and facile method to quantify almonertinib in rat plasma using ultra-performance liquid chromatography-tandem mass spectrometry. The study found that Paxlovid significantly inhibited the metabolism of almonertinib and increased its exposure. This research provides valuable insights into the metabolic profile of almonertinib and suggests the need for further human trials to validate the results.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Robert J. Young
Summary: The rule of 5, developed by Lipinski et al., has had a profound influence on drug discovery, but its guidelines have been applied too strictly by some without understanding the underlying statistics. Recent developments in physicochemical estimations and new measurements, predictions, and principles have taken drug discovery beyond the rule of 5.
EXPERT OPINION ON DRUG DISCOVERY
(2023)
Article
Engineering, Environmental
Ouli Xiao, Minmin Li, Deyong Chen, Jieyin Chen, Jesus Simal-Gandara, Xiaofeng Dai, Zhiqiang Kong
Summary: The degradation kinetics of pesticides in honeysuckle were investigated, and it was found that pesticides had short half-lives in honeysuckle while showing high processing factors during drying and decoction. The ecotoxicities of degradation products were evaluated, and special populations such as children require careful risk control in terms of dietary exposure.
JOURNAL OF HAZARDOUS MATERIALS
(2022)
Article
Chemistry, Multidisciplinary
Bruno Linclau, Zhong Wang, Benjamin Jeffries, Jerome Graton, Rodrigo J. Carbajo, Davy Sinnaeve, Jean-Yves Le Questel, James S. Scott, Elisabetta Chiarparin
Summary: Efficient drug discovery relies on optimizing bioactivity and compound properties such as lipophilicity, guided by efficiency metrics; the use of conformer-specific lipophilicities is a less explored strategy; optimizing lipophilicity values for different conformers can create a novel avenue in drug discovery.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Analytical
You-Rim Lee, Seungyeon Lee, Sohyen Kwon, Jiyeong Lee, Hee-Gyoo Kang
Summary: Metabolomic research has been conducted in various fields, but the combination of forensic science and metabolomics is rare. This study identified and validated metabolite markers for determining the age of bloodstains within a week post-bleeding. These markers could be used as innovative tools for reconstructing crime scenes and suggesting initial investigative direction.
ANALYTICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Yury Kostyukevich, Elena Stekolshikova, Anna Levashova, Anna Kovalenko, Anna Vishnevskaya, Anton Bashilov, Albert Kireev, Boris Tupertsev, Lidiia Rumiantseva, Philipp Khaitovich, Sergey Osipenko, Eugene Nikolaev
Summary: The administration of low doses of D2O has been used for decades to investigate metabolic pathways and measure compound turnover rate. Previously, the uptake of deuterium in lipids was mainly studied using GC-MS instruments, but recent untargeted LC-MS/MS lipidomics approaches have been employed. In this study, the deuterium uptake in over 500 lipids was investigated in 13 organs and body fluids of mice after 4 days of 100% D2O administration. The highest deuteration was observed in the liver, plasma, and lung, while lower levels were found in the brain and heart. The incorporation of deuterium in palmitic and stearic fragments in lipids was demonstrated using MS/MS, but not in the corresponding free forms. The results were analyzed based on lipid metabolic pathways.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Heba Badr, Ron Blutrich, Kaitlin Chan, Jiefei Tong, Paul Taylor, Wen Zhang, Ran Kafri, Hannes L. Rost, Ming-Sound Tsao, Michael F. Moran
Summary: Proteome analysis revealed co-expressed upregulated metabolism proteins highly conserved between primary NSCLC and patient-derived xenograft tumors. The encoded genes of these proteins are associated with the survival of NSCLC patients, suggesting their role in driving NSCLC through metabolic processes.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Chemistry, Applied
Sijia Wang, Runan Li, Fengshou Dong, Yongquan Zheng, Yuanbo Li
Summary: In this study, a method was established to determine the concentrations of cyetpyrafen and its metabolites in various matrices. The results showed that cyetpyrafen undergoes extensive transformation in a soil-strawberry system.
Article
Biochemical Research Methods
Yongfen Ma, Xiaowei Chen, Huma Javeria, Zhenxia Du
Summary: A new method for screening LogD or LogP in the drug discovery stage is presented, utilizing the shake flask method combined with rapid LC-MS/MS bioanalysis and a sample pooling approach. The method is evaluated by comparing the measured LogD values of single and pooled compounds, showing good correlation and indicating the simultaneous measurement of at least 37 compounds with acceptable accuracy. Additionally, the sample pooling method significantly reduces the number of bioanalysis samples when compared to the conventional shake flask method.
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
(2023)
Article
Chemistry, Analytical
Josefine Schulz, Robin Michelet, Jan F. Joseph, Markus Zeitlinger, Fabian Schumacher, Gerd Mikus, Charlotte Kloft
Summary: The pharmacokinetics of Voriconazole (VRC) is not fully understood, posing challenges for its therapeutic use. A bioanalytical LC-MS/MS assay was developed and validated to simultaneously quantify VRC and its metabolite in human plasma, ultrafiltrate, and microdialysate. The assay demonstrated accuracy and precision, and its suitability was shown in clinical and in vitro experiments. This method allows for increased sampling in vulnerable populations and provides a higher temporal resolution in microdialysis studies, which contributes to a better understanding of VRC's pharmacokinetics and therapy optimization.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2022)
Article
Pharmacology & Pharmacy
Siqi Ren, Jingjing Liu, Yunwen Xue, Mei Zhang, Qiwei Liu, Jie Xu, Zunjian Zhang, Rui Song
Summary: Development of a rapid UHPLC-MS/MS method to investigate and compare the apparent permeability of Saikosaponins (SSs) and their corresponding deglycosylated derivatives (SGs) revealed that SGs showed improved permeability compared to parent compounds, suggesting higher in vivo absorption. Efflux ratio (ER) values indicated active uptake of SSd and SGs, while passive diffusion of SSa and SSb2.
JOURNAL OF PHARMACEUTICAL ANALYSIS
(2021)
Article
Chemistry, Analytical
Zhendong Chen, Liang Li, Yan Zhan, Yifan Zhang, Haiyan Liu, Jianjun Zou, Dafang Zhong
Summary: Henagliflozin is a specific inhibitor of SGLT2 proposed for T2DM treatment. This study identified 8 metabolites of henagliflozin in human plasma and urine, focusing on the glucuronidation and O-deethylation pathways. A LC-MS/MS method was developed for quantification of M5-1, M5-2, and M5-3 in human plasma.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2021)
Article
Plant Sciences
Fernanda R. R. Castro-Moretti, Jean-Christophe Cocuron, Humberto Castillo-Gonzalez, Efrain Escudero-Leyva, Priscila Chaverri, Oliveiro Guerreiro-Filho, Jason C. C. Slot, Ana Paula Alonso
Summary: The aim of this study was to develop a high-throughput workflow to identify and quantify plant polyphenols. A method was optimized for extracting over 40 families of phytochemicals and a high-throughput metabolomic platform was developed to identify and quantify 184 polyphenols in 15 min.
FRONTIERS IN PLANT SCIENCE
(2023)
Article
Automation & Control Systems
Miguel Figueiredo, Stamatios Giannoukos, Serge Rudaz, Renato Zenobi, Julien Boccard
Summary: A novel chemometric approach, called Rebalanced ASCA (RASCA), is proposed to analyze high-dimensional data from unbalanced designs of experiments. It was compared with other methods and found to provide consistent results and handle unbalanced designs effectively, producing unbiased parameter estimators and rigorously orthogonal effect matrices.
JOURNAL OF CHEMOMETRICS
(2023)
Article
Neurosciences
David Pamies, Tatjana Vujic, Domitille Schvartz, Julien Boccard, Cendrine Repond, Carolina Nunes, Serge Rudaz, Jean-Charles Sanchez, Victor Gonzalez-Ruiz, Marie-Gabrielle Zurich
Summary: This study found that the activation of human ReN-derived astrocytes is closely related to energy metabolism, and increased glycolysis may be considered as an endpoint for detecting astrocyte activation by potentially neurotoxic compounds in vitro. This is important for studying the mechanisms of neurotoxicity and the direct effects of chemicals on astrocytes.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Chemistry, Analytical
Gioele Visconti, Julien Boccard, Max Feinberg, Serge Rudaz
Summary: In the past two decades, liquid chromatography coupled to mass-spectrometry (LC-MS) has become the gold standard for qualitative and quantitative analysis of small molecules. The design of calibration curves has evolved with instrumental advances, introducing innovative approaches to improve accuracy and efficiency. This tutorial covers the advances in LC-MS quantitative analysis for small molecules in complex matrices, including fundamental aspects in calibration, modern methodologies, and applications. The importance of international guidelines for analytical method validation that align with calibration strategies and analytical instrumentation is emphasized.
ANALYTICA CHIMICA ACTA
(2023)
Article
Biochemistry & Molecular Biology
Antonina Klimenko, Robin Huber, Laurence Marcourt, Dmitry Tabakaev, Alexey Koval, Salim Sh. Dautov, Tatyana N. N. Dautova, Jean-Luc Wolfender, Rob Thew, Yuri Khotimchenko, Emerson Ferreira Queiroz, Vladimir L. L. Katanaev
Summary: Through metabolite analysis, we have identified five new chlorin compounds from Ophiura sarsii and O. ooplax, demonstrating their potential applications in photodynamic therapy.
Article
Biochemical Research Methods
Sergey Girel, Davy Guillarme, Szabolcs Fekete, Serge Rudaz, Victor Gonzalez-Ruiz
Summary: Monitoring the central carbon metabolism network using LC-MS analysis is challenging due to the diverse chemical nature of analytes and non-specific adsorption on metal surfaces. In this study, different chromatographic methods were investigated for untargeted analysis of energy metabolism-related analytes in biological samples, and the best performance was achieved with sulfoalkylbetaine HILIC. Additionally, an extra hydrophilic modulation may be necessary for better resolution of carboxylic acids in zHILIC mode.
JOURNAL OF CHROMATOGRAPHY A
(2023)
Article
Microbiology
Alexandre Le Loarer, Remy Marcellin-Gros, Laurent Dufosse, Jerome Bignon, Michel Frederich, Allison Ledoux, Emerson Ferreira Queiroz, Jean-Luc Wolfender, Anne Gauvin-Bialecki, Mireille Fouillaud
Summary: Despite advances in medicine and technology, deadly diseases are still a threat to humanity. To find effective treatments, research is focusing on unexplored habitats with unique biodiversity, such as the marine environment. Studies have shown the potential of bioactive compounds from marine organisms in treating diseases.
Article
Chemistry, Analytical
Miguel de Figueiredo, Jonas Saugy, Martial Saugy, Raphael Faiss, Olivier Salamin, Raul Nicoli, Tiia Kuuranne, Serge Rudaz, Francesco Botre, Julien Boccard
Summary: A novel approach is proposed to generate individual adaptive reference ranges by simultaneously monitoring multiple biomarkers, improving the detection of testosterone administration. The combination of urine and serum biomarkers reduces the number of false-negatives, highlighting the complementarity between urine and blood sampling in doping control.
ANALYTICA CHIMICA ACTA
(2023)
Article
Chemistry, Analytical
Miguel de Figueiredo, Serge Rudaz, Julien Boccard
Summary: This study proposes a new method to handle unbalanced groups in multifactorial experimental designs. The method extends a prior rebalancing strategy and uses ANOVA for decomposition, while preserving within-group variation and orthogonal effect matrices, avoiding confusion of effects and improving model interpretation. It can be combined with any multivariate method for high-dimensional data analysis.
ANALYTICA CHIMICA ACTA
(2023)
Article
Chemistry, Analytical
Gioele Visconti, Miguel de Figueiredo, Oriane Strassel, Julien Boccard, Nicolas Vuilleumier, David Jaques, Belen Ponte, Serge Rudaz
Summary: The study proposes a multitargeted internal calibration (MTIC) approach for accurate quantitative analysis in liquid chromatography-mass spectrometry (LC-MS) for endogenous compound quantification when there is no blank matrix available. The approach integrates stable isotope labeled (SIL) standards as internal calibrants, allowing simultaneous quantification of analytes using within sample calibration. The developed MTIC workflow demonstrates reliable quantification of metabolites related to chronic kidney disease (CKD) in small serum or plasma samples.
ANALYTICAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Florentin Coppey, Cedric Schelling, Jean-Luc Veuthey, Pierre Esseiva
Summary: This article introduces an innovative technology or technology architecture that integrates a handheld device, Viavi MicroNIR, with a cloud-based system. By analyzing cannabis specimens, the transformative impact of this technology on field operators is demonstrated, with a particular focus on the system's ability to distinguish between CBD-type and THC-type cannabis. The near-infrared (NIR) spectra show remarkable congruence with the reference analytical method. The article highlights the advantages of this application in expediting routine illicit drug analysis and alleviating the burden on laboratories, providing laboratory personnel with additional time for more complex cases, thus enhancing overall efficiency.
HELVETICA CHIMICA ACTA
(2023)
Article
Chemistry, Analytical
William Bello, Julian Pezzatti, Markoulina Berger-Gryllaki, Serge Rudaz, Farshid Sadeghipour
Summary: Prefilled plastic packaging in hospital pharmacy is beneficial for preventing waste, errors, contamination, and accidents. A new sensitive method based on LC-HRMS has been developed to analyze plastic additives in the prefilled drug solutions prepared in hospital pharmacies. Plastic additives can be rapidly identified and their toxicology can be assessed using this method.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2023)
Article
Chemistry, Analytical
Elena Tobolkina, David Pamies, Marie-Gabrielle Zurich, Serge Rudaz, Victor Gonzalez-Ruiz
Summary: In this study, the limitations of CE-MS in untargeted metabolomics were overcome by using standardized CE-MS conditions and automatically converting CE-MS files into electrophoretic mobility scale. CE-MS-based metabolomics was used to analyze low-volume samples generated during the toxicological risk assessment, resulting in the annotation of 68 metabolites. Multivariate analysis was performed to compare the metabolic profiles induced by different compounds.
MICROCHEMICAL JOURNAL
(2023)
Article
Plant Sciences
Hugo Morin, Aurore Chetelat, Stephanie Stolz, Laurence Marcourt, Gaetan Glauser, Jean-Luc Wolfender, Edward E. Farmer
Summary: The connections between wound-response electrical signaling and jasmonate synthesis activation are not known. This study investigated the remodeling of jasmonate precursor pools in the leaf vasculature of Arabidopsis thaliana in response to injury. Metabolomics and NMR were used to analyze galactolipids and jasmonate precursors in undamaged and wounded plants, while DAD1-LIKE LIPASEs (DALLs) that regulate these precursor levels were identified. The study found a novel galactolipid, sn-2-OPDA-MGMG, containing the jasmonate precursor 12-oxo-phytodienoic acid (OPDA), in the veins. It was discovered that electrical signals triggered a rapid reduction of vascular OPDA-MGMGs, sn-2-OPDA-MGMG, and free OPDA pools. In mutant plants with reduced DALL2 function, there was a failure to build resting vascular sn-2-OPDA-MGMG and OPDA pools, resulting in less production of jasmonoyl-isoleucine (JA-Ile) upon wounding. DALL3 acted to suppress excessive JA-Ile production, while dall2 dall3 double mutants greatly reduced jasmonate signaling in leaves distal to wounds.
Article
Agriculture, Multidisciplinary
Adriano Rutz, Jean-Luc Wolfender
Summary: Recent developments in mass spectrometry-based metabolite profiling have allowed for unprecedented qualitative coverage of complex biological extract composition. However, the use of electrospray ionization in metabolite profiling leads to multiple artifactual signals for a single analyte. In this study, we developed a generic qualitative and quantitative approach using a combination of liquid chromatography-mass spectrometry (LC-MS) and Charged Aerosol Detection (CAD) to annotate and contextualize features in a high-resolution tandem MS dataset. Signals not attributed to CAD peaks are considered minor metabolites. This approach enables the automatic assessment of the composition of single natural extracts or broader collections, facilitating new ingredient registrations or natural-extracts-based drug discovery campaigns.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Article
Chemistry, Analytical
Gioele Visconti, Miguel de Figueiredo, Oriane Strassel, Julien Boccard, Nicolas Vuilleumier, David Jaques, Belen Ponte, Serge Rudaz
Summary: Accurate quantitative analysis in liquid chromatography-mass spectrometry (LC-MS) can be achieved by generating calibration curves in the same matrix as the study sample. The multitargeted internal calibration (MTIC) approach, which utilizes stable isotope labeled (SIL) standards as internal calibrants, is a promising method for the quantification of endogenous compounds. A study using MTIC workflow was conducted to quantify metabolites related to chronic kidney disease (CKD) in serum or plasma samples. The results demonstrated the feasibility of this approach for absolute quantification of endogenous biomarkers.
ANALYTICAL CHEMISTRY
(2023)
