Targeted metabolomics: Liquid chromatography coupled to mass spectrometry method development and validation for the identification and quantitation of modified nucleosides as putative cancer biomarkers

Godoy, Adriana Teixeira; Eberlin, Marcos N.; Simionato, Ana Valéria Colnaghi

doi:10.1016/j.talanta.2019.120640

Cited by 26 publications

(9 citation statements)

References 57 publications

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“…This outcome could be consistent with the synthetic challenges we experienced in the synthesis of N-Me-4PY. When we applied this chemistry to nicotinamide riboside (NR), we detected 2PYR [41] and 6PYR [42,43], the two isomers of 4PYR (Figure 3), along with nicotinamide, the product formed from NR hydrolysis. These outcomes indicate that the NQO2-catalyzed over-oxidation of NRH favors one isomer, 4PYR, and occurs via a mechanism that differs from Fenton chemistry as it is more regioselective.…”

Section: Resultsmentioning

confidence: 99%

The Biochemical Pathways of Nicotinamide-Derived Pyridones

Hayat

Sonavane

Makarov

et al. 2021

IJMS

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As catabolites of nicotinamide possess physiological relevance, pyridones are often included in metabolomics measurements and associated with pathological outcomes in acute kidney injury (AKI). Pyridones are oxidation products of nicotinamide, its methylated form, and its ribosylated form. While they are viewed as markers of over-oxidation, they are often wrongly reported or mislabeled. To address this, we provide a comprehensive characterization of these catabolites of vitamin B3, justify their nomenclature, and differentiate between the biochemical pathways that lead to their generation. Furthermore, we identify an enzymatic and a chemical process that accounts for the formation of the ribosylated form of these pyridones, known to be cytotoxic. Finally, we demonstrate that the ribosylated form of one of the pyridones, the 4-pyridone-3-carboxamide riboside (4PYR), causes HepG3 cells to die by autophagy; a process that occurs at concentrations that are comparable to physiological concentrations of this species in the plasma in AKI patients.

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Section: Resultsmentioning

confidence: 99%

The Biochemical Pathways of Nicotinamide-Derived Pyridones

Hayat

Sonavane

Makarov

et al. 2021

IJMS

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“…Before LC-MS analysis, solid phase extraction (SPE) can be used for the prepurification of purine bases or nucleosides, as described in the research works referenced in Table 2 . Suitable SPE approaches include C18 [ 70 ], porous graphitic carbon (PGC) [ 71 , 72 ], phenylboronic acid (PBA) [ 73 , 74 ], hydrophilic lipophilic balances (HLB) [ 70 , 75 , 76 , 77 , 78 ], cation exchange (e.g., MCX) [ 79 ], and weak anion exchange (WAX) [ 80 ] phases. The comparison of nucleotide purification by (i) polymeric materials with polar and non-polar functionalities (ABN, ENV+, and HLB), (ii) ion-exchange sorbents (anionic (MAX) and cationic (MCX)), and (iii) an affinity sorbent (Affi-gel, to retain compounds with a cis-diol group in their structure) indicated that HLB provided the highest versatility for the purification of the largest panel of nucleotides [ 75 ].…”

Section: Analytical Workflows To Quantify the Intended Chemical Action Of Temozolomide In Glioblastomamentioning

confidence: 99%

Approaching Sites of Action of Temozolomide for Pharmacological and Clinical Studies in Glioblastoma

et al. 2021

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Temozolomide (TMZ), together with bulk resection and focal radiotherapy, is currently a standard of care for glioblastoma. Absorption, distribution, metabolism, and excretion (ADME) parameters, together with the mode of action of TMZ, make its biochemical and biological action difficult to understand. Accurate understanding of the mode of action of TMZ and the monitoring of TMZ at its anatomical, cellular, and molecular sites of action (SOAs) would greatly benefit precision medicine and the development of novel therapeutic approaches in combination with TMZ. In the present perspective article, we summarize the known ADME parameters and modes of action of TMZ, and we review the possible methodological options to monitor TMZ at its SOAs. We focus our descriptions of methodologies on mass spectrometry-based approaches, and all related considerations are taken into account regarding the avoidance of artifacts in mass spectrometric analysis during sampling, sample preparation, and the evaluation of results. Finally, we provide an overview of potential applications for precision medicine and drug development.

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“…Thus, in the untargeted discovery of metabolomics information on metabolome, identification of pattern and “metabolic fingerprinting” are performed to classify phenotypes and their associated interaction pathways 30 . On the other hand, in targeted metabolomics approaches, also known as “biased or directed metabolomics” or “metabolic profiling,” a quantitative analysis of known or targeted metabolites is performed to explore perturbations in metabolic pathways and classification of phenotypes 31 . Thus, the metabolomics approach has a broad scope in establishing diagnostic markers of various neurodegenerative diseases and, thus, has the potential for a more personalised therapeutic approach.…”

Section: Introductionmentioning

confidence: 99%

Metabolomics of neurological disorders in India

Gupta

Sharma

2021

Analytical Science Advances

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Metabolomics is the comprehensive study of the metabolome and its alterations within biological fluids and tissues. Over the years, applications of metabolomics have been explored in several areas, including personalised medicine in diseases, metabolome‐wide association studies (MWAS), pharmacometabolomics and in combination with other branches of omics such as proteomics, transcriptomics and genomics. Mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy are the major analytical techniques widely employed in metabolomics. In addition, MS is coupled with chromatography techniques like gas chromatography (GC) and liquid chromatography (LC) to separate metabolites before analysis. These analytical techniques have made possible identification and quantification of large numbers of metabolites, encompassing characterization of diseases and facilitating a systematic and rational therapeutic strategy based on metabolic patterns. In recent years, the metabolomics approach has been used to obtain a deeper insight into the underlying biochemistry of neurodegenerative disorders and the discovery of biomarkers of clinical implications. The current review mainly focuses on an Indian perspective of metabolomics for the identification of metabolites and metabolic alterations serving as potential diagnostic biomarkers for neurological diseases including acute spinal cord injury, amyotrophic lateral sclerosis, tethered cord syndrome, spina bifida, stroke, Parkinson's disease, glioblastoma and neurological disorders with inborn errors of metabolism.

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Targeted metabolomics: Liquid chromatography coupled to mass spectrometry method development and validation for the identification and quantitation of modified nucleosides as putative cancer biomarkers

Cited by 26 publications

References 57 publications

The Biochemical Pathways of Nicotinamide-Derived Pyridones

The Biochemical Pathways of Nicotinamide-Derived Pyridones

Approaching Sites of Action of Temozolomide for Pharmacological and Clinical Studies in Glioblastoma

Metabolomics of neurological disorders in India

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