Matrix ion suppression

Compared with LC/MS/MS methods, nanoelectrospray/MS/MS methods offer additional benefits such as no sample carry-over and low sample and solvent consumptions. The major concerns surrounding columnless analysis of biological samples are matrix ion suppression and direct interference from endogenous components or metabolites of the dosed compound. Therefore, an extensive sample clean-up process must be in place to ensure the accuracy and precision of the assay. A nine-fold gain in terms of sample throughput was achieved with a nanoelectrospray/MS/ MS method that produced accuracy, precision, and detection limits comparable to those of a traditional LC/MS/MS method.14... 

Direct injections using RAM or TFC have simplified sample preparation and increased throughput. Matrix ion suppression was greatly reduced or eliminated in several cases compared with traditional off-line sample cleanup procedures such as PPT, SPE, and LLE. Method development time was minimized with generic methods15 that suit most applications. Detailed applications can be found in a recent review.8... 

A unique property of LC/API/MS is the extent to which the analyte signal is affected by the sample matrix or the existence of co-eluting analytes. This property can have a profound influence on sensitivity and assay reproducibility. Because of matrix-ion suppression, it is not possible to estimate extraction recovery by comparison of the signal from a neat sample to an extracted sample. This is because the reduction in signal represents the combined effects of recovery and ion suppression. As first shown by Buhrman et al., quantitative assessment of extraction efficiency is made by spiking the neat sample into an extracted blank and comparison of the result to a similar sample spiked before extraction [120]. Conversely, the extent of ion suppression is obtained by the comparison of the signals for a neat unextracted sample to the same neat solution spiked into an extracted matrix blank. 

A variety of improvements with regard to HPLC-MS have occurred. The 2x 30 mm (4 p) supplanted the longer wider column and 2-3 min run times were achieved with ballistic gradients [9], Questions regarding matrix ion suppression and issues with coeluting endogenous and exogenous impurities resulted in issues with both discovery (non-GLP) and development (GLP) assays [10-12],... 

There are several drawbacks with this approach. The loss of separation resolution at higher linear velocities results in issues ranging from matrix ion suppression to... 

FIGURE 8.4 Matrix ion suppression effect in precipitated rat plasma vs. mobile phase A using the 1 min ballistic gradient. (From Dunn-Meynell, K.W. et al., Rapid Commun. Mass Spectrom., 19, 2905, 2005. With permission.)... 

Turnipseed et al. described a method for the multi-class residue determination of P-Iactams, sulfonamides, tetracyclines, fluoroquinolones, and macroiides in milk and other dairy products. The sample preparation combines extraction with acetonitrile, clean-up with Oasis HLB cartridges, and ultrafiltration using molecular weight cut-off filters to improve the overall performance of the analysis. Acceptable recoveries were obtained for sulfanomides, macroiides, and quinolones (>70%) however, recoveries were rather low for tetracyclines (50-60%) and P-lactams (<50%). Despite the extensive clean-up procedure, significant matrix ion suppression was observed for many compounds, making it necessary to include matrix-matched calibration standards for quantification purposes. 

Table 2 lists the most commonly used matrix, ion suppression system, and solvent system for analyzing common dendrimers. Here we present example systems employed, which can serve as a starting point in the selection of a matrix. Most of these systems have been developed via trial and error approaches as there exists a multitude of combinations used in MALDI analysis. ... 

Dendrimer type End group Matrix Ion suppression Solvent system References... 

Hgure 4 Schematic diagram of the experimental setup for the study of matrix ion-suppression effects in electrospray ionization mass spectrometry. (Based on Bonfiglio R et at. (1999) Rapid Communications in Mass Spectrometry 13 1175.)... 

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