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The design of a new ion mobility mass spectrometer (IMMS) is presented. This new design features an ambient-pressure resistive glass ion mobility drift tube (RGIMS) coupled to a high-resolution time-of-flight mass spectrometer (TOFMS) by an enhanced interface that includes two segmented quadrupoles. The interface design demonstrates an increase in sensitivity while maintaining high resolving power typically achieved for ambient-pressure IMS drift tubes. Performance of the prototype instrument was evaluated and the analytical figures of merit for standard solutions as well as complex samples such as human blood were determined. For a 3 [micro]M solution of caffeine, the peak was collected in 36 s and gave a response of 10 counts/s. The detection limit (defined as 1 count/s) was calculated to be 300 nM concentration of caffeine from the response rate from the 36 s run. Controlled fragmentation of caffeine was achieved through adjustment of voltages applied on the interface lenses. Over 300 tentative metabolites were detected in human blood along with 80 isomers/isobars with ion counts > 5. Isotope ratios from extracted mass spectra of selected mobility peaks were used to identify selected metabolite compounds. High separation power for both IMS (resolving power, [t.sub.d]/[DELTA][t.sub.w1/2], was 85) and MS (mass resolving power, m/[DELTA]m, maximum was 7000 with a mass accuracy between 2 and 10 ppm) was measured. Developed software for data acquisition, control and display allowed flexibility in instrument control, data evaluation and visualization. 10.1021/ac1017259

Ambient pressure ion mobility time-of-flight mass spectrometry (IMMS) has recently emerged as a rapid and efficient analytical technique for applications to metabolomics. Ah important application of metabolomics is to monitor metabolome shifts caused by stress due to toxin exposure, nutritional changes, or disease. The research presented in this paper uses IMMS to monitor metabolic changes in rat lymph fluid caused by dietary stresses over time. Extracts of metabolites found in the lymph fluid collected from dietary stressed rats were subjected to analysis by electrospray (ESI) IMMS operated both in positive and negative ion detection mode. Metabolites detected were tentatively identified based on their mass to charge ratio (m/z). In one sample, 1180 reproducible tentative metabolite ions were detected in negative mode and 1900 reproducible tentative metobolite ions detected in positive mode. Only biologically reproducible ions, defined as metabolite ions that were measured in different rats under the same treatment, were analyzed to reduce the complexity of the data. A metabolite peak list including m/z, mobility, and intensity generated for each metabolome was used to perform principle component analysis (PCA). Dynamic changes in metabolomes were investigated using principle components PC1 and PC2 that described 62% of the variation of the system in positive mode and 81% of the variation of the system in negative mode. Analysis of variance (ANOVA) was performed for PC 1 and PC2 and means were statistically evaluated. Profiles of intensifies were compared for tentative metabolite ions detected at different times before and after the rats were fed to identify the metabolites that were changing the most. Mobility-mass correlation curves (MMCC) were investigated for the different classes of compounds.

The effects of above-ambient pressure on ion mobility on resolving power, resolution, and ion current were investigated using a small, stand-alone ion mobility spectrometer (IMS). This work demonstrates the first example of ion mobility spectrometry at pressures above ambient. Ion mobility spectra of chemical warfare agent (CWA) stimulant dimethyl methylphosphonate (DMMP) and several other standard compounds are shown for super-ambient conditions. The IMS was operated at pressures from 700 to 4560 Torr. An optimal resolving power was obtained at a specific voltage as a function of pressure, with higher optimal resolving powers obtained at higher voltages, as predicted from standard IMS theory. At high pressures, however, resolving power did not increase as much as theory predicted, presumably due to ion clustering. Nevertheless, an increase in pressure was found to improve resolution in IMS. One example where high pressure improved resolution was the separation of cyclohexylamine ([K.sub.0] = 1.83) and 2-hexanone ([K.sub.0] = 1.86) (where [K.sub.0] is the reduced mobility value). The product ions of these two compounds could not be separated at ambient pressure but could be nearly baseline separated when the pressure of the buffer gas was raised to 2280 Torr. Total ion current was also examined at pressures from ambient up to 4560 Torr. Total ion current, when investigated with pressure, was found to reach a maximum, initially rising with increased pressure.

This article introduces the concept of chiral ion mobility spectrometry (CIMS) and presents examples demonstrating the gas-phase separation of enantiomers of a wide range of racemates including pharmaceuticals, amino acids, and carbohydrates. CIMS is similar to traditional ion mobility spectrometry, where gas-phase ions, when subjected to a potential gradient, are separated at atmospheric pressure due to differences in their shapes and sizes. In addition to size and shape, CIMS separates ions based on their stereospecific interaction with a chiral gas. In order to achieve chiral discrimination by CIMS, an asymmetric environment was provided by doping the drift gas with a volatile chiral reagent. In this study (S)-(+)-2-butanol was used as a chiral modifier to demonstrate enantiomeric separations of atenolol, serine, methionine, threonine, methyl [alpha]-glucopyranoside, glucose, penicillamine, valinol, phenylalanine, and tryptophan from their respective racemic mixtures.