Expanding the linear dynamic range for quantitative liquid chromatography-high resolution mass spectrometry utilizing natural isotopologue signals

• Less abundant isotopologue ions were utilized to decrease detector saturation.
• A 25–50 fold increase in the upper limit of dynamic range was demonstrated.
• Linear dynamic range was expanded without compromising mass resolution.

The linear dynamic range (LDR) for quantitative liquid chromatography–mass spectrometry can be extended until ionization saturation is reached by using a number of target isotopologue ions in addition to the normally used target ion that provides the highest sensitivity. Less abundant isotopologue ions extend the LDR: the lower ion abundance decreases the probability of ion detector saturation. Effectively the sensitivity decreases and the upper limit of the LDR increases. We show in this paper that the technique is particularly powerful with a high resolution time of flight mass spectrometer because the data for all ions are automatically acquired, and we demonstrated this for four small organic molecules; the upper limits of LDRs increased by 25–50 times.

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