Unexpected observation of ion suppression in a liquid chromatography/atmospheric pressure chemical ionization mass spectrometric bioanalytical method

Abstract

Ion suppression is a well-known phenomenon in electrospray ionization (ESI) mass spectrometry. These suppression effects have been shown to adversely affect the accuracy and precision of quantitative bioanalytical methods using ion spray. Such suppression effects have not been as well defined in atmospheric pressure chemical ionization (APCI) and there is some debate whether these effects actually occur in the ionization process using APCI. Here an example is described where clear ion suppression was observed during studies on a model compound and three metabolites using APCI liquid chromatography/tandem mass spectrometry (LC/MS/MS).

An overview of matrix effects in liquid chromatography–mass spectrometry

“…Therefore, a shift from ESI to APCI is an excellent way to reduce ME (Barnes et al, 1995;Matuszewsky, Constanzer, & Chavez-Eng, 1998King et al, 2000;Schuhmacher et al, 2003;Vanderford et al, 2003;Ching, Zhang, & Karnes, 2004). However, as previously reported, the occurrence of a signal suppression phenomenon has also been shown with APCI (Liang et al, 2003;Mei et al, 2003;Sangster et al, 2004;Zhao & Metcalfe, 2008).…”

“…However, some studies on bioanalytical and environmental samples have demonstrated that APCI is not completely free from ME (Liang et al, 2003;Mei et al, 2003;Sangster et al, 2004;Zhao & Metcalfe, 2008). The main reason why APCI is sometimes less prone to ME than ESI can be found in the way each technique produces the charged analyte.…”

“…A first mechanism can be found in the formation of solid precipitates due to the presence of nonvolatile sample components (King et al, 2000). Sangster and coworkers suggest that differences in electron affinity between compounds in the GP can modify the efficiency of charge transfer from the corona-discharge needle (Sangster et al, 2004).…”

Sensitivity “Hot Spots” in the Direct Analysis in Real Time Mass Spectrometry of Nerve Agent Simulants

“…The factors that affect the prevailing ionization pathway depend on the presence and type of sample matrix, solvents and contaminants, the DART gas composition, and the chemical properties of the analyte [17]. Even with optimized parameters, there is some evidence that DART may sometimes succumb to deleterious matrix effects involving ion suppression [18] when the depletion point of reactive species has been reached [19]. Ion suppression is expected to be present to some extent in all ion direct generation approaches, and affect sensitivity and dynamic range by preferentially decreasing analyte signals.…”

Principles and Applications of LC-MS/MS for the Quantitative Bioanalysis of Analytes in Various Biological Samples

“…APCI-MS is less susceptible to matrix effects than ESI-MS and, however, the occurrence of matrix effects has also been shown with APCI (Dams et al, 2003;Sangster et al, 2004;Niessen et al, 2006). In addition, the APCI interface was more susceptible to matrix effects than the ESI interface for the same instrument.…”