Expanding the linear dynamic range for multiple reaction monitoring in quantitative liquid chromatography–tandem mass spectrometry utilizing natural isotopologue transitions

We describe a method for expanding the linear dynamic range for multiple reaction monitoring (MRM) in quantitative liquid chromatography/tandem mass spectrometry (LC–MS/MS) using additional transitions for isotopologues. In addition to the regular transition for the highest possible sensitivity, a transition corresponding to the less abundant isotopologue ions was utilized. This decreases saturation at the ion detector; the sensitivity reduction increases the upper dynamic limit. We demonstrated this for a rat plasma assay for a candidate flavor compound; the linear dynamic range increased by an order of magnitude from 3 to 6000 ng/mL with the regular MRM alone to 3–60,000 ng/mL using additionally the isotopologue transition.