The isotope distribution: A rose with thorns

Abstract

The isotope distribution, which reflects the number and probabilities of occurrence of different isotopologues of a molecule, can be theoretically calculated. With the current generation of (ultra)‐high‐resolution mass spectrometers, the isotope distribution of molecules can be measured with high sensitivity, resolution, and mass accuracy. However, the observed isotope distribution can differ substantially from the expected isotope distribution. Although differences between the observed and expected isotope distribution can complicate the analysis and interpretation of mass spectral data, they can be helpful in a number of specific applications. These applications include, yet are not limited to, the identification of peptides in proteomics, elucidation of the elemental composition of small organic molecules and metabolites, as well as wading through peaks in mass spectra of complex bioorganic mixtures such as petroleum and humus. In this review, we give a nonexhaustive overview of factors that have an impact on the observed isotope distribution, such as elemental isotope deviations, ion sampling, ion interactions, electronic noise and dephasing, centroiding, and apodization. These factors occur at different stages of obtaining the isotope distribution: during the collection of the sample, during the ionization and intake of a molecule in a mass spectrometer, during the mass separation and detection of ionized molecules, and during signal processing.

Discovering Nature’s Fingerprints: Isotope Ratio Analysis on Bioanalytical Mass Spectrometers

“…This includes diverse factors that can alter the observed isotope distribution during sample preparation, ionization, mass analysis and detection as well as signal processing. 71 Important factors that need to be studied and controlled for are:…”

“…• Linear dynamic range of an instrument for specific isotope ratio analyses 47,71 • Isotopic exchange or fractionation during sample preparation (e.g., in reactions with solvents, chemical derivatization) 72 • Near-isobaric impurities that may overlap with the desired m/z values of the analyte 73 • Isotopic fractionation associated with (liquid) chromatography 74 • Kinetic isotope effects and changes in the precursor and product ions population in fragmentation reactions that can influence the isotope signatures 75 If remaining technical issues can be adequately addressed, we may be seeing applications of isotopic techniques that have long been envisioned by isotope researchers.…”

“…While the sources of artifacts in traditional isotope ratio analysis are well understood, the same cannot be said for this emerging area of isotope ratio analysis. This includes diverse factors that can alter the observed isotope distribution during sample preparation, ionization, mass analysis and detection as well as signal processing . Important factors that need to be studied and controlled for are: Linear dynamic range of an instrument for specific isotope ratio analyses , Isotopic exchange or fractionation during sample preparation (e.g., in reactions with solvents, chemical derivatization) Near-isobaric impurities that may overlap with the desired m / z values of the analyte Isotopic fractionation associated with (liquid) chromatography Kinetic isotope effects and changes in the precursor and product ions population in fragmentation reactions that can influence the isotope signatures …”

A compositional data model to predict the isotope distribution for average peptides using a compositional spline model

“…A review paper that lists several applications and limitations of the isotope distribution has recently been published by Claesen et al. [11].…”

“…Moreover, Valkenborg et al proposed a method that models the consecutive ratios of isotope peaks using a polynomial model, ignoring the compositional nature of the data [9]. A review paper that lists several applications and limitations of the isotope distribution has recently been published by Claesen et al [11].…”