Matrix effects demystified: Strategies for resolving challenges in analytical separations of complex samples

Abstract

Matrix effects can significantly impede the accuracy, sensitivity, and reliability of separation techniques presenting a formidable challenge to the analytical process. It is crucial to address matrix effects to achieve accurate and precise measurements in complex matrices. The multifaceted nature of matrix effects which can be influenced by factors such as target analyte, sample preparation protocol, composition, and choice of instrument necessitates a pragmatic approach when analyzing complex matrices. This review aims to highlight common challenges associated with matrix effects throughout the entire analytical process with emphasis on gas chromatography‐mass spectrometry, liquid chromatography‐mass spectrometry, and sample preparation techniques. These techniques are susceptible to matrix effects that could lead to ion suppression/enhancement or impact the analyte signal at various stages of the analytical workflow. The assessment, quantification, and mitigation of matrix effects are necessary in developing any analytical method. Strategies can be implemented to reduce or eliminate the matrix effect by changing the type of ionization, improving extraction and clean‐up methods, optimization of chromatography conditions, and corrective calibration methods. While development of an effective strategy to completely mitigate matrix effects remains elusive, an integrated approach that combines sample preparation, analytical extraction, and effective instrumental analysis remains the most promising avenue for identifying and resolving matrix effects.

Multiresidue analysis of bat guano using GC-MS/MS

“…Within GC-MS/MS measurements, matrix effects occur as matrix-induced response enhancement and are a well-known phenomenon. Matrix components may mask active sites in the liner and column, increasing analyte transfer to the analyser [ 53 – 55 ]. This effect can result in different measured peak areas in matrix compared to solvent samples of the same actual concentration.…”

Optimizing Analysis Methods: Rapid and Accurate Determination of Cuaminosulfate Residues with LC-MS/MS Based on Box–Behnken Design Study

“…ME means that other components in the matrix will interfere with the quantification of target analyte when they are co-ionized [ 32 ]. When |ME| ≥ 50%, ME was strong [ 33 , 34 ]. Therefore, the influence of the substrate on the results cannot be ignored, and the calibration should be performed for cuaminosulfate according to the external matrix-matched standards to eliminate the ME and obtain more accurate quantification in all samples.…”

Evolution of Green Sample Preparation: Fostering a Sustainable Tomorrow in Analytical Sciences

“…For instance, it can be highlighted the high concentration of proteins, acids, and salts, 173 which causes in most cases matrix effects, significantly impeding accuracy, sensitivity, and reliability. 174 Additionally, the sample availability is limited in most cases (except for urine), the sampling can be invasive, and compatibility with the instrumental setup must be always addressed. 173 This class of samples should be handled with special care taking into account the physiological conditions so as not to affect or alter both the matrix/patient and target compounds.…”

“…Biological samples are generally difficult matrices to analyze due to their complex composition (low ratio analyte/interferent), analyte stability, and material integrity being mandatory the application of robust sample preparation methods. For instance, it can be highlighted the high concentration of proteins, acids, and salts, which causes in most cases matrix effects, significantly impeding accuracy, sensitivity, and reliability . Additionally, the sample availability is limited in most cases (except for urine), the sampling can be invasive, and compatibility with the instrumental setup must be always addressed .…”