Biomolecules Quantitative Mass Spectrometry upon Isotopic Dilution

Dear Colleagues,

Life science research linked to health societal issues requires, at one stage, the quantitative monitoring of a biomolecule of interest present at trace level in a complex biological matrix. For instance, drug discovery and drug development together with therapeutic drug and biomarker monitoring rely on state-of-the-art analytical sciences in the context of pharmacology, pharmacy, toxicology, and clinic applications to improve the efficiency and safety of medicines or diagnosis for the benefit of patients. Thus, one can mention that the discovery of new biomarkers permits to better understand mechanisms of action in several pathologies, to enhance prognosis by development of more sensitive diagnostic tools that are efficient for early stages pathology detection, to identify therapeutic targets and improve the mechanism of action of drugs. In all of these applications, the targeted molecules to be monitored belong to various classes of organic compounds ranging from very small structures, like amino acids, for instance, to heavy biomolecules such as peptides, proteins, and lipids, inferring very different physicochemical properties. Therefore, any quantitative methodology has to be robust, specific, sensitive, reproducible, and validated with caution, especially regarding its accuracy/precision. In addition, the ability to multiplex simultaneous analyses allows a greater adaptability to high throughput screening.

Among all analytical approaches dedicated to quantitation including immunoassays or radioactivity and fluorescence measurements, mass spectrometry (MS) associated with the stable isotope dilution (SID) methodology offers a unique opportunity to perform sensitive accurate quantitative experiments. Similarly to radioactivity and fluorescence measurements that necessitate appropriate compound labeling to insert either a radioactive element or a fluorescent moiety, ISD-MS quantitative strategies count on stable isotope insertion in the structure of the analyte of interest to keep all physicochemical properties unchanged, except the overall molecular mass. This isotopically-labeled molecule/biomolecule, either designed by chemical engineering through a dedicated derivatization reaction (chemical labeling) or produced during metabolic processes in cell cultures (metabolic labeling), acts as a reference (internal standard) for accurate relative concentration measurements. Moreover, specificity and sensitivity of quantification are achieved by tandem mass spectrometry (MS/MS) usually conducted on triple quadrupole mass analyzers (QqQ) upon collision-induced dissociation (CID) with multiple transition monitoring (MRM) acquisition mode hyphenated to separative techniques such as gas chromatography (GC), liquid chromatography (LC) or capillary electrophoresis (CE), which represent key points for complex biological matrix analyses.

This Special Issue deals with the development of new analytical procedures/labeling methodologies dedicated to the quantification of biomolecules in complex biological matrix (blood, plasma, urine, cells, tissues, etc.) by mass spectrometry in accordance with isotopic dilution strategies. This Special Issue will provide the opportunity to share knowledge about state-of-the-art targeted biomolecule quantitative mass spectrometry analysis, which is essential for scientists from various disciplines (biology, chemistry, biochemistry) involved in research projects dealing with biomarker or drug monitoring.

Prof. Dr. Christine Enjalbal
Guest Editor

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• Pharmacy
• Pharmacology
• Pharmacokinetics
• ADME
• Bioanalyses
• Environment
• Diagnosis
• Proteomic
• Metabolomic
• Targeted quantification
• Stable isotope dilution
• Chemical labeling
• Metabolic labeling
• Tandem mass spectrometry
• MS/MS
• Triple quadrupole
• QqQ
• MRM
• CID