Evaluation of the potential use of hybrid LC–MS/MS for active drug quantification applying the ‘free analyte QC concept’

What is it about?

After administration of biologics a significant fraction of the drug can be present in a complexed and thus neutralized form, bound to soluble target and/or antidrug antibodies. Since free/active drug may sometimes be the most relevant species allowing a correct interpretation of PK/PD data, active drug assays become increasingly important throughout the whole drug development and feasibility could be shown with ligand binding assays (LBA). In recent years LC-MS/MS methods for the quantification of large molecules are applied more frequently and a combination of specific extraction methods theoretically enable active drug analysis by hybrid-LC-MS methods. The drug capture part is the critical factor for an accurate active drug determination independent of whether the detection is performed by an LBA or by mass spectrometry (hybrid LC-MS/MS method).

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