MSACL Conference Schedule

Ion Suppression and Other Interferences in the Qualitative and Quantitative LC-MS/MS Analysis of Biological Fluids

Wed 9:00 AM - Session: Toxicology

Tom Annesley

Because of the specificity of mass spectrometry, it is commonly believed that sample cleanup and chromatographic separation play much lesser roles in the success of analyses compared to other types of detectors. While generally true, results from published studies have shown that matrix effects can significantly alter the quality and types of results obtained by liquid chromatography-mass spectrometry (LC-MS). These effects can be observed as suppression or enhancement of the ionization process in electrospray (ESI) or atmospheric pressure chemical ionization (APCI). While the full range of causes of ion suppression and enhancement remains to be solved, a common source is components that may be present in the biological sample, as well as buffers, and even co-eluting drugs or metabolites. Even LC instrument design and column selection can make an assay more prone to encountering ion suppression.

Clinical laboratories are accustomed to analyzing serum and urine, and many validated LC-MS and LC-MS/MS assays have been designed to minimize substantial matrix effects. In clinical and forensic toxicology, however, additional biological samples types may arise, including gastric contents, meconium, hair, degraded, aged or dried blood, saliva, vitreous fluid, and tissues. These specimens present a different challenge in sample preparation, analysis, and the potential for ion suppression or enhancement. In some cases ESI has been reported to the more susceptible, while some reports have found APCI to be affected.

This presentation will cover the basics of matrix effects in LC-MS, illustrating different approaches that have been recommended for evaluating ion suppression. Examples of the potential effects of specimen type, dosage vehicles, solvents, sample preparation, MS instrument settings, analyte/matrix mass ratios, LC instrument design, choice of internal standard, and mode of chromatography on the quality of results will be used to highlight the many subtleties of ion suppression.