An Electrospray Ionization-Ion Mobility Spectrometer as Detector for High-Performance Liquid Chromatography

Abstract

The application of electrospray ionization (ESI) ion mobility (IM) spectrometry on the detection end of a high-performance liquid chromatograph has been a subject of study for some time. So far, this method has been limited to low flow rates or has required splitting of the liquid flow. This work presents a novel concept of an ESI source facilitating the stable operation of the spectrometer at flow rates between 10 μL mn(-1) and 1500 μL min(-1) without flow splitting, advancing the T-cylinder design developed by Kurnin and co-workers. Flow rates eight times faster than previously reported were achieved because of a more efficient dispersion of the liquid at increased electrospray voltages combined with nebulization by a sheath gas. Imaging revealed the spray operation to be in a rotationally symmetric multijet mode. The novel ESI-IM spectrometer tolerates high water contents (≤90%) and electrolyte concentrations up to 10mM, meeting another condition required of high-performance liquid chromatography (HPLC) detectors. Limits of detection of 50 nM for promazine in the positive mode and 1 μM for 1,3-dinitrobenzene in the negative mode were established. Three mixtures of reduced complexity (five surfactants, four neuroleptics, and two isomers) were separated in the millisecond regime in stand-alone operation of the spectrometer. Separations of two more complex mixtures (five neuroleptics and 13 pesticides) demonstrate the application of the spectrometer as an HPLC detector. The examples illustrate the advantages of the spectrometer over the established diode array detector, in terms of additional IM separation of substances not fully separated in the retention time domain as well as identification of substances based on their characteristic Ims.

Real‐Time Reaction Monitoring of an Organic Multistep Reaction by Electrospray Ionization‐Ion Mobility Spectrometry

“…New information can appear owing to the complementary separation on the LC column and in the drift tube. Because of the different time scales of HPLC (minutes) and IM spectrometry (milliseconds), both methods can be combined easily, yielding 2 D spectra consisting of the dimensions of retention and drift time . A 2 D spectrum of the consecutive N ‐alkylation from 3 to 4 is shown in Figure at the reaction time corresponding to the maximum intensity of the disubstituted species (5 min).…”

“…All IM spectra were recorded with a home‐built ESI‐IM spectrometer, which has been described in detail previously . The spectrometer is divided into four sections.…”

“…Herein, the capability of ESI‐IM spectrometry was evaluated, both as a stand‐alone method and in combination with HPLC, for qualitative and quantitative reaction monitoring. The enhancement of the separation power through the combination of HPLC with ESI‐IM spectrometry is based on our previous work . A three‐step reaction consisting of a Williamson ether synthesis followed by a hydrogenation and an N ‐alkylation reaction was chosen for the characterization of reaction monitoring by ESI‐IM spectrometry.…”

IR-MALDI ion mobility spectrometry

“…An in-house built drift tube IM spectrometer previously described by Zühlke et al [26] was employed to characterize the IR-MALDI source. It was slightly modified to result in two configurations: first, the orthogonal electrospray ionization source was simply replaced with the IR-MALDI source in order to investigate the effects of the ion gate.…”

“…For comparison purposes in detection limits, our in-house built ESI-IM spectrometer, previously described by Zühlke et al [26], and a linear ion trap mass spectrometer (LTQ XL, Thermo Scientific, Waltham, MA, USA) equipped with the IR-MALDI source, were employed. In the setup of the IR-MALDI source, the droplet is arranged directly in front of the inlet capillary of the mass spectrometer.…”