Carefully Count Your Ions! A Guide to Direct Quantitation with Mass Spectrometry

This tutorial is intended as an educational resource covering the application of mass spectrometry (MS) to quantitative analysis. MS is a widely used instrumental technique in both academic and industrial settings. Because MS analysis functions by weighing molecules, it measures a fundamental physical property, providing qualitative information that is independent of the matrix, method, and instrument. With the additional capabilities of tandem MS (MS/MS), unparalleled qualitative characterization is possible by MS alone at low detection limits. This is often where the story stops, however. In some cases, direct MS quantitative analysis (i.e., without chromatography) can be equally advantageous. Direct MS is a method of choice in situations where speed, detection limit, and solvent/sample consumption are premium. Using the determination of the caffeine content in beverages as a test case, best practices for MS quantitation are explained and explored. Quantitative performance of paper spray (PS) and nanoelectrospray ionization (nESI), using either a triple quadrupole (QqQ) or quadrupole ion trap (QIT) mass spectrometer, is compared.