Biological Matrix Effects in Quantitative Tandem Mass Spectrometry-Based Analytical Methods: Advancing Biomonitoring

Abstract

The ability to quantify levels of target analytes in biological samples accurately and precisely, in biomonitoring, involves the use of highly sensitive and selective instrumentation such as tandem mass spectrometers and a thorough understanding of highly variable matrix effects. Typically, matrix effects are caused by co-eluting matrix components that alter the ionization of target analytes as well as the chromatographic response of target analytes, leading to reduced or increased sensitivity of the analysis. Thus, before the desired accuracy and precision standards of laboratory data are achieved, these effects must be characterized and controlled. Here we present our review and observations of matrix effects encountered during the validation and implementation of tandem mass spectrometry-based analytical methods. We also provide systematic, comprehensive laboratory strategies needed to control challenges posed by matrix effects in order to ensure delivery of the most accurate data for biomonitoring studies assessing exposure to environmental toxicants.

Matrix Effects and Application of Matrix Effect Factor

“…Since, matrix effects were first observed for ESI MS in 1990s, several mechanisms have been proposed [5,6,9,10]. These include matrix components preventing analyte from gaining access to the charge, competing with analytes to gain charge, interfering with analyte's ability to remain charged in the gas phase, increasing surface tension of droplet or increasing electric resistance.…”

“…The changes in liquid phase could result in the alteration of the amount of charged ions in the gas phase. In addition, matrix components or mobile-phase additives that act as ion-pairing reagents usually reduce ionization efficiency and result in low response [9].…”

“…The changes in liquid phase could result in the alteration of the amount of charged ions in the gas phase. In addition, matrix components or mobile-phase additives that act as ion-pairing reagents usually reduce ionization efficiency and result in low response [9].Based on the available literature and our experiences, atmospheric pressure chemical ionization (APCI) and atmospheric pressure photoionization (APPI) sources have less matrix effects than an ESI source, because APCI utilizes gas-phase ion-molecule reactions and APPI utilizes hot solvent vapor for desorption. For APCI, the neutral molecular analyte is first transferred into the gas phase through liquid evaporation in a flow of heated gas [11,12], and then ionization occurs by chemical ionization in the gas phase [13].…”

Analytical Validation of Clopidogrel in Human Plasma Through Ultrahighperformance Liquid Chromatography-Tandem Mass Spectrometry

“…The matrix factor value obtained in the high concentration was 85.053%, meaning that there was ions suppression [14,15]. The internal standard matrix factor value was 99.463%, meaning that there was a slight decrease in the ions.…”

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“…Hydrogels (for example, polyethylene glycol) have strength similar to that of cartilaginous tissues; however, their biodegradability is rather low. On the whole, the properties of all these compounds are much inferior to the biological matrix parameters 6 .…”