Determination and correction of retention time and mass/charge shifts in LC-MS experiments

A method for acquiring Liquid Chromatography Mass Spectrometry (LC-MS) data for a plurality of analytes within an unknown sample, the method comprising:

• performing a control experiment comprising an LC-MS analysis of a plurality of analytes within a control sample, thereby generating control data;
• recording the control data;
• choosing a chunk size that comprises a range, ΔRT, of chromatographic retention times and a range, Δm/z, of mass-to-charge values;
• choosing a chunk of the control data (control chunk) having the chunk size;
• storing a set of data that includes the control chunk;
• scheduling tentative retention time windows for the plurality of analytes within the unknown sample based on the chromatographic retention times determined from the control data, each tentative retention time window comprising a respective start time and a respective stop time;
• performing at least a portion of an experiment comprising an LC-MS analysis of the unknown sample, thereby generating a sample chunk of LC-MS spectral data, the sample chunk comprising a range of retention times that is less than ΔRT within the tentative retention time windows;
• calculating a cross-correlation function between the sample chunk and the control chunk;
• identifying, using the calculated cross-correlation function, a retention-time shift of the experiment comprising the LC-MS analysis of the unknown sample with respect to the control experiment;
• estimating m/z shift values of the sample chunk of the LC-MS spectral data of the unknown sample, relative to control data of the control chunk, based on results of a two dimensional cross-correlation calculation between the the control chunk and the sample chunk;
• generating a modified retention time window by adjusting a tentative retention time window in accordance with the identified retention-time shift;
• and
• acquiring mass spectrometry data from the unknown sample at a retention time window that is associated with the adjusted retention time window and using the estimated m/z values.