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. (C) 2011 Elsevier B.V. All rights reserved.