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

Abstract

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.

Quantitative mass spectrometry methods for pharmaceutical analysis

“…Co-eluting matrix substances will influence the constant detector response and can thus be used to correct for suppression or enhancement [61]. Post-extraction spiking and post-column infusion matrix [54,56]. The high selectivity of a chromatographic separation combined with mass spectrometric detection allows the multicomponent analysis of difficult samples.…”

“…Finally, validation experiments can be performed by a different operator to assess robustness [62]. [56,63,64]. An overview of these agencies is reviewed by Wille et al and Gonzalez et al [63,64].…”

“…In these articles, different hypotheses have been postulated; however, the exact mechanism of ion suppression or enhancement remains unresolved. MEs are influenced by multiple factors such as analyte characteristics, type of matrix, sample preparation procedure, chromatographic conditions, type of ionization and mass spectrometer settings as described in table 1 [7,19,[52][53][54][55][56]. It is very likely that these features have a synergic effect on the ionization; however, it cannot be ruled out that MEs can be allocated to only one cause [55].…”

Zopiclone degradation in biological samples : Characteristics and consequences in forensic toxicology

“…Analytical methods should therefore be validated for drug identification or quantification, under the conditions of intended use. Method validation includes several analytical parameters; selectivity, calibration model, accuracy (bias) and precision, limit of detection (LOD), lower limit of quantification (LLOQ), recovery/extraction efficiency and parameters affected by specimen composition such as matrix effects and stability [17][18][19][20][21][22]. Analytical result showing presence or absence of a drug in the specimen yields information relevant to the time of analysis and the stability of the drug in the actual matrix has to be considered in connection with result interpretation [23].…”

Postmortem Biochemistry and Toxicology

“…Moreover, LC-MS may suffer from either ion enhancement, or ion suppression from co-eluting sample components [16], phenomena that may not be compensated for by the use of (expensive) stable-isotope labelled internal standards [17]. It should be remembered that many drugs are administered as either single enantiomers, or racemic mixtures, and yet achiral analytical methods are often all that is available for the analysis of biological specimens.…”