Ion Suppression: A Major Concern in Mass Spectrometry - - Chromatography Online
Ion Suppression: A Major Concern in Mass Spectrometry


LCGC North America
Volume 24, Issue 5

Ion suppression is one form of matrix effect that liquid chromatography–mass spectrometry (LC–MS) techniques suffer from, regardless of the sensitivity or selectivity of the mass analyzer used. Ion suppression negatively affects several analytical figures of merit, such as detection capability, precision, and accuracy. The limited knowledge of the origin and mechanism of ion suppression makes this problem difficult to solve in many cases. Over the past decade and a half since the response-reducing phenomenon was exposed, however, protocols have been developed not only to test for its presence but also to account for its effects and eliminate the risk of ion suppression altogether. Because there is no universal solution for the matrix effect, some of the viable options are discussed briefly in this tutorial, which alone or in combination can help regain the quality of LC–MS analysis for the particular matrix–analyte combination. Two commonly used techniques to detect the presence of the matrix effect are illustrated. Modifying instrumental components and parameters, chromatographic separation, and sample preparation are all considered as means of reducing or possibly eliminating ion suppression. A variety of calibration techniques for compensating the effects of the phenomenon also are discussed.


Figure 1: Multiple reaction monitoring chromatograms for a constant postcolumn infusion of analyte (phenacetin). For the lower trace, protein precipitation blank plasma was injected, while the upper trace exhibits the chromatogram for an injection of pure mobile phase. The difference between the two traces directly shows the effect of endogenous plasma components on the analyte´s response. (Chromatographic traces reproduced from reference 25 by courtesy of John Wiley and Sons.)
Liquid chromatography–mass spectrometry (LC–MS) and tandem mass spectrometry (LC–MS-MS) have been established as the most sensitive and selective analytical techniques for biological samples. Starting in the early 1990s, however, many studies also have reported difficulties with reproducibility and accuracy when analyzing small quantities of analytes in complex samples such as biological fluids (1–3). Kebarle and Tang (2) originally described the matrix effect phenomenon as the result of coeluted matrix components, affecting the detection capability, precision, or accuracy for the analytes of interest. Ion suppression appears as one particular manifestation of matrix effects, which is associated with influencing the extent of analyte ionization (Figure 1). This change often is observed as a loss in response, thus, the term ionization suppression. However, depending upon the type of sample, it also can be observed as an increase in the response of the desired analyte (4). In this tutorial, the mechanism and origin of ion suppression will be investigated, as well as ways to validate the presence and circumvent or compensate for the effects in LC–MS.


ADVERTISEMENT

RELATED CONTENT
Detection of Doping Agents by LC–MS and LC–MS-MS
Techniques for Structure Elucidation of Unknowns: Finding Substitute Active Pharmaceutical Ingredients in Counterfeit Medicines
High-Throughput Quantitative LC-MS-MS Assays by On-Line Extraction Using Monolithic Support
Alternatives in the Face of Chemical Diversity
How Little Feb 07
blog comments powered by Disqus
LCGC E-mail Newsletters
Global E-newsletters subscribe here:




 

LCGC COLUMNISTS 2014

Column Watch: Ron Majors, established authority on new column technologies, keeps readers up-to-date with new sample preparation trends in all branches of chromatography and reviews developments. LATEST: When Bad Things Happen to Good Food: Applications of HPLC to Detect Food Adulteration


Perspectives in Modern HPLC: Michael W. Dong is a senior scientist in Small Molecule Drug Discovery at Genentech in South San Francisco, California. He is responsible for new technologies, automation, and supporting late-stage research projects in small molecule analytical chemistry and QC of small molecule pharmaceutical sciences. LATEST: HPLC for Characterization and Quality Control of Therapeutic Monoclonal Antibodies


MS — The Practical Art: Kate Yu brings her expertise in the field of mass spectrometry and hyphenated techniques to the pages of LCGC. In this column she examines the mass spectrometric side of coupled liquid and gas-phase systems. Troubleshooting-style articles provide readers with invaluable advice for getting the most from their mass spectrometers. LATEST: Radical Mass Spectrometry as a New Frontier for Bioanalysis


LC Troubleshooting: LC Troubleshooting sets about making HPLC methods easier to master. By covering the basics of liquid chromatography separations and instrumentation, John Dolan is able to highlight common problems and provide remedies for them. LATEST: How Much Can I Inject? Part I: Injecting in Mobile Phase


More LCGC Columnists>>

LCGC North America Editorial Advisory Board>>

LCGC Europe Editorial Advisory Board>>

LCGC Editorial Team Contacts>>


Source: LCGC North America,
Click here