Method To Reduce Chemical Background Interference in Atmospheric Pressure Ionization Liquid Chromatography−Mass Spectrometry Using Exclusive Reactions with the Chemical Reagent Dimethyl Disulfide

Abstract

The interference of chemical background ions (chemical noise) has been a problem since the inception of mass spectrometry. We present here a novel method to reduce the chemical noise in LC-MS based on exclusive gas-phase reactions with a reactive collision gas in a triple-quadrupole mass spectrometer. Combined with the zero neutral loss (ZNL) scan of a triple-quadrupole mass spectrometer, the reactive chemical noise ions can be removed because of shifts of mass-to-charge ratios from the original background ions. The test on various classes of compounds with different functional groups indicates a generic application of this technique in LC-MS. The preliminary results show that a reduction of the level of LC-MS base-peak chromatographic baseline by a factor up to 40 and an improvement of the signal-to-noise ratio by a factor up to 5-10 are achieved on both commercial and custom-modified triple-quadrupole LC-MS systems. Application is foreseen in both quantitative and qualitative trace analysis. It is expected that this chemical noise reduction technique can be optimized on a dedicated mass spectrometric instrumentation which incorporates both a chemical reaction cell for noise reduction and a collision stage for fragmentation.

Alternative reagents for chemical noise reduction in liquid chromatography-mass spectrometry using selective ion-molecule reactions

“…The collision gas inlet of the mass spectrometers was modified to introduce a volatile chemical reagent into the radio-frequency (RF)-only quadrupole (Q2) collision cell. This modification allows freeze, pump, and thaw cycles needed to degas the liquid chemical reagents and a quick switch between the chemical reagent and the normal collision gas nitrogen [18].…”

“…Positive ESI ionization was used. Details of similar experiments have been published previously [18]. Briefly, to study the gas-phase reactions, ions of the background interference or the protonated analytes were first mass-selected by Q1 and then allowed to undergo reactive collisions with the reagent present in the second quadrupole Q2 (RF-only).…”

“…In our recent study [17,18] DMDS has been discovered to react very selectively with the vast majority of background ions and applied as the first neutral reagent to reduce chemical noise in API-LC-MS while it is combined with the mass filtering functions of quadrupole analyzers in MS/MS mode. Under the conventional ZNL or Q-3 full-scan MS condition, some clustertype background noise may also undergo dissociation reaction during collisions if the collision energy is sufficiently high [21].…”

“…Under the conventional ZNL or Q-3 full-scan MS condition, some clustertype background noise may also undergo dissociation reaction during collisions if the collision energy is sufficiently high [21]. However, in our approach [18], the collision energy has been kept sufficiently low to prevent dissociation of any analytes. It has been proven that noise reduction with DMDS is predominantly the result of selective reactions with background ions.…”

“…In our previous study we have developed a novel noise-reduction technique [17,18] based on selective reactions of the neutral reagent dimethyl disulfide (DMDS) with background ions in LC-MS, where apparently the significant structure characteristics of ionic noise [4], compared with that of conventional protonated species, have played a crucial role resulting in different reactivities. Both the cluster-type background ions and fragment intermediates of contaminants react very selectively with DMDS to form products with a different m/z value.…”