Increasing the linear dynamic range in LC-MS: Is it valid to use a less abundant isotopologue?

Stephen Trobbiani, Peter Stockham, Timothy Scott

    Research output: Contribution to journalArticlepeer-review

    12 Citations (Scopus)


    Liquid chromatography-mass spectrometry (LC–MS) has quickly become the analytical method of choice in forensic toxicology laboratories due to its ability to detect a very wide range of compounds in a single analysis. One of the major limitations of LC–MS however, is a relatively limited linear dynamic range for quantitation. A new approach to combating this problem is to use the [+1M + H]+ isotope mass peak for quantitation, thereby reducing saturation at the detector and extending the linear range. This is particularly useful in full-scan applications, such as quadrupole-time-of-flight (QTOF) mass spectrometry, where the isotopic mass peaks are acquired as a matter of course. Due to the variation in abundance of naturally occurring isotopes for common elements, especially 13C, this technique has the potential to lead to additional quantitative error. Through a review of published isotope ratio mass spectrometry data, we have assessed this potential for error and found that it is likely to be less than 2% and unlikely to be more than 4%, although this may not apply to compounds containing high numbers of nitrogen or sulphur atoms. This additional potential error must be considered before using this technique as it may not be appropriate for all applications. We have deemed it fit for purpose for our application and demonstrate the applicability of this technique to a quantitative LC-TOF method.

    Original languageEnglish
    Pages (from-to)1630-1636
    Number of pages7
    JournalDrug Testing and Analysis
    Issue number10
    Early online date2016
    Publication statusPublished - Oct 2017


    • isotope ratio
    • isotopologue
    • LC–MS, high-resolution mass spectrometry
    • linear range


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