The present invention relates to methods for continuous or near-continuous separation and purification of samples, particularly biological samples, to reduce the number or volume of non-targeted analytes in those samples to enable improved mass spectrometric analysis of analytes of interest, and apparatuses for conducting those methods, utilizing a transport agent with a core domain and a binding domain, the transport agent exceeding 200 kiloDaltons or 10 nm, and the binding domain targeted to the analytes of interest, in conjunction with size-exclusion based chromatography to separate the transport agent-analyte of interest complex from non-targeted analytes that are not bound, or are only non-specifically bound, to the transport agent.