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

Boschmans, Jasper; Lemière, Filip; Sobott, Frank

doi:10.1016/j.chroma.2017.02.015

Cited by 9 publications

(5 citation statements)

References 58 publications

(68 reference statements)

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“…Several reports have shown that solvents affect the formation of tautomers detected by IM-MS. − Chandran et al found solvent effects must be thoroughly evaluated before a validated “standard” protocol for the quantitative determination of an analyte can be developed and recommended. In addition, Morsa et al detected the mobility peaks of acetonitrile adducts of electrophilic benzylium cations using the electrospray ionization source by trapped ion mobility spectrometer (TIMS).…”

Section: Introductionmentioning

confidence: 99%

Influence Exerted by the Solvent Effect on the Mobility Peak of 1,8-Naphthalic Anhydride in Ion Mobility Spectrometry

Zhang

Wang

Zheng

et al. 2022

J. Am. Soc. Mass Spectrom.

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The collision cross-section (CCS) values of ions determined by ion mobility-mass spectrometry (IM-MS) can be used to deduce the shape and size of the ions. For each compound, as well as its isomer or tautomer, a unique arrival time peak was obtained in extracted ion mobility (EIM) spectra, which corresponded to a specific CCS value. However, the generation of solvated ions by electrospray ionization (ESI) increases the number of mobility peaks, which makes the EIM spectra difficult to interpret. In this study, solvent clusters formed by acetonitrile and methanol around 1,8-naphthalic anhydride (1,8-NA) cations ([C12H6O3 + H]+ 1,8‑NA) were investigated using trapped ion mobility spectrometry-time-of-flight mass spectrometry (TIMS-TOF MS). The effects of infusion flow rate, nebulizer gas pressure, drying gas rate, and drying gas temperature on the formation of solvent clusters from acetonitrile and methanolic solution were systematically studied. The formation of solvent clusters was observed with infusion flow rates increased, which was manifested by the larger experimental CCS values of [C12H6O3 + H]+ 1,8‑NA. Acetonitrile tended to form solvent clusters around ions more readily than methanol. These solvent clusters were stable enough to be detected by TIMS, but they cannot survive under ion activation conditions of mass spectrometry (MS). Increasing the nebulizer gas pressure seems to be a better way to eliminate the formation of solvent clusters in TIMS-TOF MS and give a “cleaner” EIM spectra. The current research demonstrates that more attention should be paid to the solvent effect on CCS values and their interpretation.

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Section: Introductionmentioning

confidence: 99%

Influence Exerted by the Solvent Effect on the Mobility Peak of 1,8-Naphthalic Anhydride in Ion Mobility Spectrometry

Zhang

Wang

Zheng

et al. 2022

J. Am. Soc. Mass Spectrom.

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“…They used a mixture of polyalanines and drug-like compounds with known DTIM CCS values to calibrate TWIM CCS values (Figure 3). Regarding the use of this technique for separation purposes in bioanalysis, some applications can be found in combination with LC as an orthogonal separation dimension [93][94][95] or as a standalone separation technique [96]. In the latter case, a rapid and sensitive method was developed for the quantification of drugs in tissue sections using matrix-assisted laser desorption ionization (MALDI) as an ionization source.…”

Section: Travelling Wave Ion Mobility Spectrometry (Twims)mentioning

confidence: 99%

Ion Mobility–Mass Spectrometry for Bioanalysis

et al. 2021

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This paper aims to cover the main strategies based on ion mobility spectrometry (IMS) for the analysis of biological samples. The determination of endogenous and exogenous compounds in such samples is important for the understanding of the health status of individuals. For this reason, the development of new approaches that can be complementary to the ones already established (mainly based on liquid chromatography coupled to mass spectrometry) is welcomed. In this regard, ion mobility spectrometry has appeared in the analytical scenario as a powerful technique for the separation and characterization of compounds based on their mobility. IMS has been used in several areas taking advantage of its orthogonality with other analytical separation techniques, such as liquid chromatography, gas chromatography, capillary electrophoresis, or supercritical fluid chromatography. Bioanalysis is not one of the areas where IMS has been more extensively applied. However, over the last years, the interest in using this approach for the analysis of biological samples has clearly increased. This paper introduces the reader to the principles controlling the separation in IMS and reviews recent applications using this technique in the field of bioanalysis.

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“…Ion mobility–mass spectrometry (IM–MS) is being increasingly used for structural characterization of small molecules, − biomolecule folds, − or even synthetic polymer folds in the gas phase. − The two-dimensional shape information obtained from IM–MS as reduced ion mobility ( K 0 ) or collision cross-section (CCS) does not offer atomic level structural characterizations. Therefore, theoretical chemistry calculations are usually coupled to the IM–MS experiments.…”

Section: Introductionmentioning

confidence: 99%

Geometric Analysis of Shapes in Ion Mobility–Mass Spectrometry

Haler

Béchet

Kune

et al. 2022

J. Am. Soc. Mass Spectrom.

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Experimental ion mobility−mass spectrometry (IM−MS) results are often correlated to three-dimensional structures based on theoretical chemistry calculations. The bottleneck of this approach is the need for accurate values, both experimentally and theoretically predicted. Here, we continue the development of the trend-based analyses to extract structural information from experimental IM−MS data sets. The experimental collision cross-sections (CCSs) of synthetic systems such as homopolymers and small ionic clusters are investigated in terms of CCS trends as a function of the number of repetitive units (e.g., degree of polymerization (DP) for homopolymers) and for each detected charge state. Then, we computed the projected areas of expanding but perfectly defined geometric objects using an in-house software called MoShade. The shapes were modeled using computer-aided design software where we considered only geometric factors: no atoms, mass, chemical potentials, or interactions were taken into consideration to make the method orthogonal to classical methods for 3D shape assessments using time-consuming computational chemistry. Our modeled shape evolutions favorably compared to experimentally obtained CCS trends, meaning that the apparent volume or envelope of homogeneously distributed mass effectively modeled the ion−drift gas interactions as sampled by IM−MS. The CCSs of convex shapes could be directly related to their surface area. More importantly, this relationship seems to hold even for moderately concave shapes, such as those obtained by geometry-optimized structures of ions from conventional computational chemistry methods. Theoretical sets of expanding beads-on-a-string shapes allowed extracting accurate bead and string dimensions for two homopolymers, without modeling any chemical interactions.

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

Cited by 9 publications

References 58 publications

Influence Exerted by the Solvent Effect on the Mobility Peak of 1,8-Naphthalic Anhydride in Ion Mobility Spectrometry

Influence Exerted by the Solvent Effect on the Mobility Peak of 1,8-Naphthalic Anhydride in Ion Mobility Spectrometry

Ion Mobility–Mass Spectrometry for Bioanalysis

Geometric Analysis of Shapes in Ion Mobility–Mass Spectrometry

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