Elsevier

Analytica Chimica Acta

Volume 627, Issue 1, 3 October 2008, Pages 71-81
Analytica Chimica Acta

Review article
Interferences and contaminants encountered in modern mass spectrometry

https://doi.org/10.1016/j.aca.2008.04.043Get rights and content

Abstract

With the invention of electrospray ionization and matrix-assisted laser desorption/ionization, scientists employing modern mass spectrometry naturally face new challenges with respect to background interferences and contaminants that might not play a significant role in traditional or other analytical techniques. Efforts to continuously minimize sample volumes and measurable concentrations increase the need to understand where these interferences come from, how they can be identified, and if they can be eliminated. Knowledge of identity enables their use as internal calibrants for accurate mass measurements. This review/tutorial summarizes current literature on reported contaminants and introduces a number of novel interferences that have been observed and identified in our laboratories over the past decade. These include both compounds of proteinaceous and non-proteinaceous nature. In the supplemental data a spreadsheet is provided that contains a searchable ion list of all compounds identified to date.

Introduction

“Scheidekunst”—the ‘art’ to separate materials into their individual components is an old German word for alchemy and analytical chemistry related sciences [1] and its basic concepts are still valid today. The last hundred years have brought enormous advances in chromatographic and other separation methods in combination with a large variety of analyte detection technologies. Any separation and detection technique has the potential to inadvertently introduce new components or contaminants into the analytical system that must be evaluated and carefully considered. It is therefore no coincidence that Modern Analytical Chemistry takes advantage of ultrapure chemicals and reagents and ultraclean sample handling containers whenever possible to minimize any potential and unwanted background interference. In addition, all routine modern analytical methods following good laboratory practices (GLP) will include blank tests such as system-, solvent-, method-, matrix- and equipment blanks [2].

With the introduction of novel ionization methods for modern mass spectrometric (MS) analysis, such as electrospray ionization (ESI) by Fenn et al. [3] and matrix-assisted laser desorption/ionization (MALDI) by Tanaka et al. [4] and independently by Karas and Hillenkamp [5], in the late eighties, scientists employing modern mass spectrometric tools face new challenges with respect to background ions that might not have played significant roles in traditional or other well-established routine analytical methodologies. The ongoing efforts to further miniaturize liquid chromatography (LC) methods [6], combinations of LC/MS [7], [8], [9], [10], [11], [12], the development of capillary electrophoresis combined with MS (CE/MS) [13] including microfluidic chip-based mass spectrometry [14], [15], [16], [17], make it easy to predict that knowledge of potential interferences and background ions will become increasingly important for successful future development of GLP-adhering methods in routine and research analytical methodologies. Miniaturization of sample transfer procedures and handling tools increases exponentially the surface to sample volume ratio and thus any interferences resulting from contaminated or background leaching surfaces will consequently also multiply.

The main focus of this review/tutorial is the introduction and description of known and identified interfering compounds that have either been reported in the scientific literature or have been observed in our own laboratories over the past decade or so. Where deemed appropriate and possible, general technical advice is included on how to minimize impacts of the described interferences.

This report does not include or further discuss specific techniques or instrumentation that allow minimization or elimination of certain background interferences, such as ion mobility MS [18], [19], high-field asymmetric waveform ion mobility spectrometry (FAIMS) [20], matrix-free laser desorption/ionization techniques [21] including desorption/ionization on silicon (DIOS) [22], desorption electrospray ionization (DESI) [23], [24], or direct analysis in real time (DART) [25]. Sources and handling of random background noise, either of electrical [26], [27], [28] or chemical nature [29], noise reduction through special software application [30], interferences introduced through degradation or metabolism of analytes/drugs during analysis [31], [32], co- or post-translational protein modifications [33], [34], background ion scrubbing via specific reactions with dimethylsulfide [35], [36], or any analyte-specific interferences are also beyond the scope of this work. We would like to refer interested readers in the above-mentioned topics to the respective cited literature and the references therein.

The supplemental data contains a spreadsheet (Microsoft-Excel) with a searchable compilation of all identified compounds to date. The list contains accurate mass-to-charge ratios for singly charged species and these can be exploited for calibration purposes in applications that require accurate mass measurements.

Section snippets

Proteinaceous interferences or contaminants

One of modern mass spectrometry's great impacts is on protein analysis and characterization. MS related techniques are now the preferred and well-established methods for protein identification [37] and quantification [38]. The complexity of biological samples requires extensive purification and separation methodologies, not only to remove non-proteinaceous components but also to address present proteins that are not of interest [39], [40]. Here we will focus on potentially interfering proteins

Non-proteinaceous interferences or contaminants

The long list of potential non-proteinaceous interferences contains both contaminants and compounds that have been recognized in traditional and established analytical methodologies, such as for example plasticizers and anti-oxidative additives, but also includes a large variety of interferences that are specific to modern mass spectrometric analysis, like matrix clusters in MALDI MS, and metal ion or solvent adducts and other solvent effects in ESI. Several instrument and sample preparation

Explanation of background ions spreadsheet

Fig. 4 shows a screen snapshot of the Excel spreadsheet available in the supplemental data. The spreadsheet contains a total of eight worksheets.

The first two worksheet tabs lead to singly charged background ion lists either in positive (+ve) or negative (−ve) mode. The positive ion list contains more than 650 species either reported in the literature or observed in our laboratories. The negative ion list contains only species that have been reported in the literature, however it should be

Conclusions

We have compiled a comprehensive database of currently known potential interferences and background-ions in modern mass spectrometry reported in the literature and observed in our own laboratories. It is clear that such a list can never be complete as modern mass spectrometry is still a young discipline enjoying rapid and dynamic growth, and new chemicals and materials are continually introduced into sample preparation assemblies and mass spectrometers themselves. Increasing emissions of

Note added in proof

Recently, Manier et al. published a more detailed identification and fragmentation study of the three quarternary ammonium compounds (listed in Table 4), employing ESI-FT-ICR-MS [98].

Acknowledgements

We thank the guest editors Dr. Patrick Limbach and Dr. David Lubman for their invitation to contribute to this special issue. Funding for mass spectrometric equipment in our laboratories has been provided by the Canadian Foundation for Innovation (CFI), the National Sciences and Engineering Research Council of Canada (NSERC), the Michael Smith Foundation for Health Research (MSFHR), the University of Alberta, Queen's University, the University of Toronto and the University of British Columbia.

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