Effect of Sample Preparation and Chromatographic Separation on Matrix Effects in Quantitative Bioanalysis
The MS response obtained from an analyte solution can differ
significantly from that same analyte in a matrix due to ion suppression
and interference from co-eluting metabolites and matrix components. Ion
suppression results from co-eluting components that compete for
ionization capacity and cause errors in accuracy and precision.
Metabolite effects occur when a drugrelated compound co-elutes with the
test compound and then fragments in the ion source of the mass
spectrometer to give a product that interferes with the MRM channel for
the drug. This will lead to an elevated response for the test compound.
These effects can sometimes be addressed by redeveloping the
chromatography, but this often increases sample analysis time. Matrix
effects should be evaluated as a part of quantitative LC/ESI-MS/MS
method development and validation. Here we investigate the use of
mixed-mode solid phase extraction and efficient chromatographic
techniques to reduce matrix effects for a range of analytes.