Although, LC–MS is one of the most sensitive and selective analytical techniques, it often suffers from matrix effects, especially when using ESI for analyzing extracts of complicated matrices [1–3]. Matrix effects are often caused by the alteration of ionization efficiency of target analytes in the presence of co-eluting compounds in the same matrix. Matrix effects can be observed either as a loss in response (ion suppression) or as an increase in response (ion enhancement). Both the ion suppression and enhancement dramatically affect analytical performance of a method [4]. Therefore, matrix effects must be evaluated when validating an LC–MS method. Since, matrix effects were first observed, efforts have been devoted to understanding the mechanisms and minimizing them [5–8]. In this commentary article, the causes of matrix effects and methods for evaluating, minimizing and/or compensating for them are discussed. A novel concept, matrix effect factor (MEF) using stable isotopically labeled internal standards (SIL-ISs) is introduced and its application is presented. Since, SIL-ISs are usually added in the very beginning of the sample preparation procedure to compensate for matrix effects and recovery, the MEF reflects any loss/gain from both the sample preparation and ‘conventional’ matrix effects caused by co-eluting components during ionization in a mass spectrometer (MS) ion source.
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