Improving sensitivity in microchip electrophoresis coupled to ESI‐MS/MS on the example of a cardiac drug mixture

Abstract

A comprehensive study for a sensitivity optimization in MCE with mass spectrometric detection is presented. As a text mixture, we chose a mixture of the cardiac drugs propranolol, bisoprolol, lidocaine, procaine and studied the effect of different chip layouts and experimental parameters with the aim of achieving both high sensitivity in MS detection and adequate chip electrophoretic separation. An important aspect was a comparison of microfluidic layouts containing various sheath-flow channels with that avoiding sheath-flow junctions on-chip. We utilized glass chips with monolithically integrated nanospray emitter tips coupled dead volume-free to an IT mass spectrometer running in fragmentation mode (MS(n) ). With this setup, detection limits down to 0.6 ng/mL for the model compound propranolol were achieved.

Chip‐based electrochromatography coupled to ESI‐MS detection

“…A possible reason could be the presence of additional MUF channels, which might act as dead volumes inducing band broadening. This was recently described for chip electrophoresis MS experiments by Schwarzkopf et al., who published a sensitivity study about the influence of different MUF layouts . The relative differences of the compounds with regard to signal intensities and peak areas if fluorescence and MS data compared are expected due to varying fluorescence quantum yields and ionization efficiencies.…”

“…In order to realize chip‐based electrochromatography with MS detection, a microfluidic glass chip was equipped with a monolithically integrated pulled nanospray emitter as described previously . A pair of MUF channels in the chip enabled electrical connection for a defined spray potential and electrical field along the column.…”

“…Different methods for chip‐MS interfacing were discussed comprehensively in recent review articles . Until now, the focus was mainly on coupling chip electrophoresis with MS . Chip‐chromatography‐MS has also become very popular since the recent success in commercialization.…”

Recent advances in CE‐MS coupling: Instrumentation, methodology, and applications

“…Belder's group proposed a multichannel design of sheath‐flow interfacing in microchip CE‐MS with six independent reservoirs with auxiliary liquids, which might be merged (before electrospraying) with the CE effluent (See Fig. ) . The purpose of this arrangement is extending of chip lifetime.…”

Recent Developments of Microchip Capillary Electrophoresis Coupled with Mass Spectrometry

“…In side channels to deliver a makeup solvent [82]. The solvent was regarded necessary in order to assist in spray formation without affecting the CE separation.…”