Aspects of matrix effects in applications of liquid chromatography-mass spectrometry to forensic and clinical toxicology—a review

In the last decade, liquid chromatography coupled to (tandem) mass spectrometry (LC–MS(−MS)) has become a versatile technique with many routine applications in clinical and forensic toxicology. However, it is well-known that ionization in LC–MS(−MS) is prone to so-called matrix effects, i.e., alteration in response due to the presence of co-eluting compounds that may increase (ion enhancement) or reduce (ion suppression) ionization of the analyte. Since the first reports on such matrix effects, numerous papers have been published on this matter and the subject has been reviewed several times. However, none of the existing reviews has specifically addressed aspects of matrix effects of particular interest and relevance to clinical and forensic toxicology, for example matrix effects in methods for multi-analyte or systematic toxicological analysis or matrix effects in (alternative) matrices almost exclusively analyzed in clinical and forensic toxicology, for example meconium, hair, oral fluid, or decomposed samples in postmortem toxicology. This review article will therefore focus on these issues, critically discussing experiments and results of matrix effects in LC–MS(−MS) applications in clinical and forensic toxicology. Moreover, it provides guidance on performance of studies on matrix effects in LC–MS(−MS) procedures in systematic toxicological analysis and postmortem toxicology.