Ion mobility spectrometry‐mass spectrometry (IMS‐MS) of small molecules: Separating and assigning structures to ions

Abstract

The phenomenon of ion mobility (IM), the movement/transport of charged particles under the influence of an electric field, was first observed in the early 20th Century and harnessed later in ion mobility spectrometry (IMS). There have been rapid advances in instrumental design, experimental methods, and theory together with contributions from computational chemistry and gas‐phase ion chemistry, which have diversified the range of potential applications of contemporary IMS techniques. Whilst IMS‐mass spectrometry (IMS‐MS) has recently been recognized for having significant research/applied industrial potential and encompasses multi‐/cross‐disciplinary areas of science, the applications and impact from decades of research are only now beginning to be utilized for “small molecule” species. This review focuses on the application of IMS‐MS to “small molecule” species typically used in drug discovery (100–500 Da) including an assessment of the limitations and possibilities of the technique. Potential future developments in instrumental design, experimental methods, and applications are addressed. The typical application of IMS‐MS in relation to small molecules has been to separate species in fairly uniform molecular classes such as mixture analysis, including metabolites. Separation of similar species has historically been challenging using IMS as the resolving power, R, has been low (3–100) and the differences in collision cross‐sections that could be measured have been relatively small, so instrument and method development has often focused on increasing resolving power. However, IMS‐MS has a range of other potential applications that are examined in this review where it displays unique advantages, including: determination of small molecule structure from drift time, “small molecule” separation in achiral and chiral mixtures, improvement in selectivity, identification of carbohydrate isomers, metabonomics, and for understanding the size and shape of small molecules. This review provides a broad but selective overview of current literature, concentrating on IMS‐MS, not solely IMS, and small molecule applications. © 2012 Wiley Periodicals, Inc., Mass Spec Rev 32:43–71, 2013

Profiling ribonucleotide modifications at full-transcriptome level: a step toward MS-based epitranscriptomics

“…In this technique, ions are dispersed on the time dimension as they travel across a low-pressure region of the instrument (Dwivedi et al 2006;Lapthorn et al 2013). The probability of undergoing lowenergy collisions with background gas is a function of their conformation, which determines the travel time.…”

Analyzing complex mixtures of drug-like molecules: Ion mobility as an adjunct to existing liquid chromatography-(tandem) mass spectrometry methods

“…Nonetheless, the analysis of samples containing co-eluting compounds and analytes with similar or identical MS properties (mass, fragmentation and/or isotope patterns) remains a frequent challenge. One of the breakthrough analytical technologies in the last decade is ion mobility-mass spectrometry (IM-MS) [1][2][3]. As a gas-phase separation technique, IM characterizes ions based on their collision cross-section (CCS; a parameter related to the ion"s rotationally averaged size, shape, total charge and charge distribution).…”

A Powerful Four-Dimensional Separation Method for Complex Samples

“…To identify analytes, the combination of ion mobility with HRMS could be a possible way. The coupling of IM to mass spectrometry started in the 1960s and experienced a strong development since the 1990s [1,2]. The first commercially available IM-MS was the Synapt HDMS system, a quadrupole/traveling-wave IMS/TOF (TWIMS) system introduced in 2006 by Waters [3].…”