Elimination Of The LC/MS Data Analysis Workflow Bottlenecks In Substance QC

Laboratory Automation (ALA 2010), Palm Springs, CA, USA, 1st – 4th March 2010, Mark Bayliss, Joseph Simpkins

Previously, within our research and services as a Clinical Research Organization we were constantly challenged with how to accurately and reliably determine the presence or absence of target substances within minimal analyst intervention. Most of these types of studies were in support of our customers performing corporate library management, support for synthetic chemists and process chemistry. While the principle and acquisition of the typical array of LC/MS, UV, ELSD and/or CLND data is relatively simple, our experience shows that reliable analysis across vendors, instruments, analytical methods and sample types creates a more intractable challenge. In the process of analyzing running millions of samples, we found a number of areas that were cause for deeper evaluation as follows: Baseline accuracy – affecting directly the integration accuracy which in turn affects area under the curve calculations (AUC) used for both purity and concentration calculations. Spectral analysis and characterization issues which often led to incorrectly assigned adducts and ionized molecules. Issues with accurate analysis and differentiation of real peaks and noise. Quantitation calculation flexibility to deal with single and multiple zone mobile phase correction and calibration. Ability to quickly find those samples which had deeper hidden issues that would actually affect the final results. For example just because a well in a microtitre plate was colored green, often did not signify that the sample was free of issues. This could be for multiple reasons including: inconclusive peak analysis for potential isomeric compounds eluting as multiple peaks. Low level extracted mass chromatograms with low signal and/or low signal to noise. Challenging elution profiles of the target substance say within a narrow time window of the major impurities where a more select purification methodology was needed. Our research and this presentation details how we approached many of these issues and brought them together into a practical application for our and other analysts. Our expectation of this poster presentation is to gather additional insights through discussion, into the issues that have been faced by other researchers in this area, how they have been solved and what additional areas of challenge remain.