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 6,000 ng/mL with the regular MRM alone to 3-60,000 ng/mL using additionally the isotopologue transition.

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http://dx.doi.org/10.1016/j.talanta.2011.09.063DOI Listing

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