An Evaluation of a Four-Channel Multiplexed Electrospray Tandem Mass Spectrometry for Higher Throughput Quantitative Analysis

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Abstract
A four-channel multiplexed electrospray inlet system (MUX) coupled to a triple quadrupole mass spectrometer was investigated as a higher throughput approach to quantitative analysis. Four discrete samples may be simultaneously analyzed by virtue of a rotating sampler with a concomitant 4-fold increase in analytical throughput. Although absolute sensitivity was reduced using the MUX interface compared with analysis using traditional single electrospray interface, reproducibility of response was shown to be comparable. Source robustness was established for the analysis of both aqueous drug standards and drugs in biological media, and linearity of response for a test compound, diazepam, was demonstrated over 2 orders of magnitude. Analyte-dependent response differences were exhibited between the four channels of the interface, and this led to the overall conclusion that samples to be compared quantitatively must be analyzed through the same sprayer. In addition, each channel must be independently calibrated to afford true quantification. Should a deuterated internal standard be employed, however, quantitative comparisons can be made across channels. An HPLC pumping system providing individual back-pressure regulation to each channel was shown to provide adequate chromatography even in the event of a channel blockage. Furthermore, following multiple injections of biological samples onto the MUX interface, an eluent flow diversion was integrated into the first part of each analytical run. This served to prevent source fouling, and thus, no detrimental effects to response reproducibility or sensitivity were observed.

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