Combating matrix effects in LC/ESI/MS: The extrapolative dilution approach

Liquid chromatography electrospray mass spectrometry – LC/ESI/MS—a primary tool for analysis of low volatility compounds in difficult matrices – suffers from the matrix effects in the ESI ionization. It is well known that matrix effects can be reduced by sample dilution. However, the efficiency of simple sample dilution is often limited, in particular by the limit of detection of the method, and can strongly vary from sample to sample.In this study matrix effect is investigated as the function of dilution. It is demonstrated that in some cases dilution can eliminate matrix effect, but often it is just reduced. Based on these findings we propose a new quantitation method based on consecutive dilutions of the sample and extrapolation of the analyte content to the infinite dilution, i.e. to matrix-free solution.The method was validated for LC/ESI/MS analysis of five pesticides (methomyl, thiabendazole, aldicarb, imazalil, methiocarb) in five matrices (tomato, cucumber, apple, rye and garlic) at two concentration levels (0.5 and 5.0 mg kg−1). Agreement between the analyzed and spiked concentrations was found for all samples. It was demonstrated that in terms of accuracy of the obtained results the proposed extrapolative dilution approach works distinctly better than simple sample dilution.The main use of this approach is envisaged for (a) method development/validation to determine the extent of matrix effects and the ways of overcoming them and (b) as a second step of analysis in the case of samples having analyte contents near the maximum residue limits (MRL).