System and method for tracking chemical entities in an LC/MS system

摘要

In complex separations, more than one entity may have the same molecular weight, to within the ability of an instrument to distinguish. Accurate mass measurements are used in light of the previously unknown regularities in retention time to determine a retention time (N pairs of values (tiB, tiBref)) (506). The retention time map allows a reference retention time to be assigned to each entity in a separation. The reference retention times, together with accurate mass measurements, can then be used to track and to compare entities (704,708) between separations.

主权项

1. A system comprising:
a liquid chromatograph into which a sample is injected to separate entities in the sample, and to determine a retention time associated with each of the one or more entities; a mass spectrometer into which the entities are input to determine a mass of each of the one or more entities; and a computer programmed to perform processing and computer code, that when executed, causes the computer to perform said processing comprising:
choosing a subset of entities from a first injection;choosing a subset of entities from a second injection;comparing the entities chosen from the first injection to those chosen from the second injection;identifying entities chosen from the first injection that match entities chosen from the second injection, wherein a first entity having a first mass and a first retention time in the first injection is considered a match for a second entity having a second mass and a second retention time in the second injection in accordance with criteria including determining a match between the first entity and the second entity if a magnitude of difference between the first mass and second mass is below a mass threshold, if a magnitude of difference between the first retention time and the second retention time is below a coarse retention time threshold and if the second entity is the only such entity in the second injection meeting the mass threshold and the coarse retention time threshold with respect to said first entity;constructing a retention time map based on the matching entities of the subsets determined by said identifying, said constructing including determining a delta retention time value and a filtered retention time drift for each pair of matching entities including a first entity from the first injection and a second entity from the second injection;assigning, based on the retention time map, reference retention times to all entities in the first injection and the second injection, wherein reference retention times are assigned to entities in the second injection using the filtered retention time drifts determined in said constructing;determining a set of differences, said set of differences including, for each pair of matching entities, a difference between the delta retention time value for said each pair and said filtered retention time drift for said each pair;determining a fine retention time threshold based on the set of differences; andtracking, in accordance with tracking criteria including the mass threshold and the fine retention time threshold that is less than the coarse retention time threshold, entities through the first and second injections using the reference retention times and mass values.