Using LC Flow Rate as a Method Development Variable for Quantitative LC-MS, presented at the 58th Conference on Mass Spectrometry and Allied Topics, May 23-27, 2010 in Salt Lake City, Utah.

There is continuing debate over the mass versus concentration dependence of ESI and APCI as well as continuing debate over the feasibility of using HPLC columns with diameters less than 2.1 mm. At the heart of both debates is the relationship between the response of the mass spectrometer and the experimental LC parameters that control MS reponse. Parameters such as mobile phase flow rate, system temperature, column length, column diameter, and mobile and stationary phase composition have been extensively studied. The relationship between LC parameters and chromatographic resolution are well understood.1 This understanding derives from concentration dependent LC detectors such as UV absorbance and GC systems that have both mass dependent detectors like flame ionization and concentration dependent detectors like thermal conductivity. We have chosen to study the effect of flow rate on the response of a triple quadrupole mass spectrometer operated in SRM mode. The practical outcome being an understanding of how flow rate specifically, and LC parameters in general can affect the limits of detection by SRM. We also hope that the data can shed some light on the questions of practically useful column diameter and the importance of the API-MS being mass or concentration dependent detector.


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