Identifying Metabolite Ions of Peptide Drugs in The Presence of An
            <i>In Vivo</i>
            Matrix Background

Cuyckens, Filip; Dillen, Lieve; Cools, W.; Bockx, Marc; Vereyken, Liesbeth; Vries, Ronald de; Mortishire‐Smith, Russell J.

doi:10.4155/bio.11.333

Cited by 18 publications

(9 citation statements)

References 18 publications

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“…If measurements for site-specific modification variants are needed, such as deamidation and oxidation variants, LC-MS is often the preferred approach [42,43]. A LBA platform is implemented only as needed or if the 'right' reagent in terms of specificity is available.…”

Section: Factors To Considermentioning

confidence: 99%

The Integration of Ligand Binding and LC-MS-Based Assays Into Bioanalytical Strategies for Protein Analysis

2014

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Both LBAs and LC-MS-based assays are reviewed and summarized for applications in quantitative protein analysis. A strategy for platform selection is proposed based on several factors that contribute to the complexities of bioanalysis of biologics. Protein types, multiple co-existing forms, post-translational modifications, and affinities to ADA, targets, and endogenous proteins need to be considered when selecting the most appropriate platform. Other factors, such as intended use of data, assay sensitivity, available reagents, and multiple analytes also impact on the choice of bioanalytical platform. At BMS, strategies for the seamless integration of both platforms are being implemented to provide not only PK/PD data of the molecules but also useful information of the amino acid structure and functional relationship of the proteins.

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Section: Factors To Considermentioning

confidence: 99%

The Integration of Ligand Binding and LC-MS-Based Assays Into Bioanalytical Strategies for Protein Analysis

2014

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“…Other untargeted approaches like isotope filtration and mass‐defect filtering (MDF) can be applied to reduce the background or to selectively filter out the ions of interest. Isotope filtration is an easy and efficient technique available in most standard instrument software packages, and is useful when the isotope distribution of the “parent” compound deviates from most background ions due to the presence of atoms with a distinct and characteristic isotope distribution such as B, Cl, Br, S, metal ions, isotopic labels, multiply‐charged ions, etc . MDF is another technique often used in drug metabolite profiling .…”

Section: The Mass Spectrummentioning

confidence: 99%

“…compound deviates from most background ions due to the presence of atoms with a distinct and characteristic isotope distribution such as B, Cl, Br, S, metal ions, isotopic labels, multiply-charged ions, etc. [23][24][25][26] MDF is another technique often used in drug metabolite profiling. 27,28 The term "mass defect" refers to the difference between the exact mass of an element or molecule and its integer value.…”

Section: Strategies To Find the Ions Of Interestmentioning

confidence: 99%

A tutorial in small molecule identification via electrospray ionization‐mass spectrometry: The practical art of structural elucidation

Vijlder

Valkenborg

Lemière

et al. 2017

Mass Spectrometry Reviews

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185

134

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The identification of unknown molecules has been one of the cornerstone applications of mass spectrometry for decades. This tutorial reviews the basics of the interpretation of electrospray ionization‐based MS and MS/MS spectra in order to identify small‐molecule analytes (typically below 2000 Da). Most of what is discussed in this tutorial also applies to other atmospheric pressure ionization methods like atmospheric pressure chemical/photoionization. We focus primarily on the fundamental steps of MS‐based structural elucidation of individual unknown compounds, rather than describing strategies for large‐scale identification in complex samples. We critically discuss topics like the detection of protonated and deprotonated ions ([M + H]+ and [M − H]−) as well as other adduct ions, the determination of the molecular formula, and provide some basic rules on the interpretation of product ion spectra. Our tutorial focuses primarily on the fundamental steps of MS‐based structural elucidation of individual unknown compounds (eg, contaminants in chemical production, pharmacological alteration of drugs), rather than describing strategies for large‐scale identification in complex samples. This tutorial also discusses strategies to obtain useful orthogonal information (UV/Vis, H/D exchange, chemical derivatization, etc) and offers an overview of the different informatics tools and approaches that can be used for structural elucidation of small molecules. It is primarily intended for beginning mass spectrometrists and researchers from other mass spectrometry sub‐disciplines that want to get acquainted with structural elucidation are interested in some practical tips and tricks.

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“…It can also be required to separate compound‐related molecules such as metabolites and degradation products. This is, for instance, the case in large molecule applications for which a biotransformation or degradation often leads to changes that are small relative to the parent drug mass and require very high MS resolution in order for these compounds to be separated from the parent drug when intact analysis is performed, as illustrated in Figure for enfuvirtide and its deamidated metabolite . When the two compounds are chromatographically unresolved, the presence of the deamidated metabolite can only be picked up with a mass resolution of at least 300,000.…”

Section: Ultra‐high‐resolution Msmentioning

confidence: 99%

Mass spectrometry in drug metabolism and pharmacokinetics: Current trends and future perspectives

Cuyckens

2018

Rapid Comm Mass Spectrometry

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Drug Metabolism and Pharmacokinetics (DMPK) is a core scientific discipline within drug discovery and development as well as post-marketing. It helps to design and select the most promising drug candidate and obtain advanced insights on the processes that control absorption, distribution, metabolism and excretion (ADME) of the final drug candidate. Mass spectrometry is one of the key technologies applied in DMPK. Therefore, the continuous advances made in the field of mass spectrometry also directly impact the way in which we investigate the ADME properties of a compound, providing us with new tools to gather more information or improve our efficiency. An overview will be given of some important current trends and future perspectives in the field.

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Identifying Metabolite Ions of Peptide Drugs in The Presence of An In Vivo Matrix Background

Cited by 18 publications

References 18 publications

The Integration of Ligand Binding and LC-MS-Based Assays Into Bioanalytical Strategies for Protein Analysis

The Integration of Ligand Binding and LC-MS-Based Assays Into Bioanalytical Strategies for Protein Analysis

A tutorial in small molecule identification via electrospray ionization‐mass spectrometry: The practical art of structural elucidation

Mass spectrometry in drug metabolism and pharmacokinetics: Current trends and future perspectives

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