Accepted: Scrivens Syngenta complex samples

Introduction

Many modern biological product formulations are made up of complex mixtures of small, organic molecules, which may include isomers, isobaric components and conformers. Characterisation and quantification of these biomolecules is often not possible using conventional mass spectrometry approaches since many of these molecules will have very similar chemical structures and mass-charge (m/z) ratios. The use of ion-mobility based mass spectrometry shape selective approaches for the characterisation of such complex formulations has a number of potential advantages. The estimated rotationally averaged collision cross sections (CCS) provide additional specific information which, when combined with effective calibration and prediction approaches, can be used to improve identification and quantitation. This enables structure/property analysis to be carried out more effectively.

Methods

Studies were performed using a cyclic ion mobility-enabled quadrupole time-of-flight (Q-cIM-oaToF) mass spectrometer. The cIM device minimizes instrument footprint whilst providing a longer, higher mobility resolution separation path; a multi-pass capability provides significantly higher resolution over a reduced (selected) mobility range; the device can be enabled for mobility separation or by-passed if not required and, the multifunctional ion entry/exit array can selectspecies within a range of mobilities, providing additional functionality. The cIM device consists of a 100 cm path length RF ion guide comprising over 600 electrodes around which T-Waves circulate to provide mobility separation. Complex formulations of industrial relevance were ionised using ESI and ASAP, mobility separated and product ion spectra obtained.

Preliminary Data

Many industrial formulations are made up of mixtures of separate components each of which can exhibit structural complexity. They may be composed of many similar products including those of the same, or similar molecular weight, which cannot be readily separated by separation science approaches. Carbon number variation and ethylene or propylene oxide distributions add to the complexity. The properties of these formulations will be dependent on the chemical structure and relative concentration of formulation components. Components of identical molecular mass in polysorbate, and other formulations have been separated by ion mobility and then fragmented for additional characterization. The rapidity and level of structural detail provided by these experiments offers a significant opportunity to develop practical screening methods for complex formulations. This requires the calculation of energy minimized three-dimensional structures and the prediction from that structure of the experimental cross section. In this work we have used a robust approach using nitrogen based calibration standards for the estimation of cross sections and the use of Avogadro and Gaussian09 for the generation of minimized structures. The trajectory method (TM) incorporated into the MOBCAL program, which incorporates charged-induced dipole interactions, has been used to predict the experimental cross sections. Where available the predicted values have been compared with published data. A range of model structures and industrially relevant formulation mixtures have been experimentally measured - and good agreement has been obtained with predicted values. The Q-cIM-oaToF mass spectrometer used in these investigations has provided a number of experimental improvements including an improved mobility resolution of Ω/∆Ω of 65 for single pass operation (and the capability of improving this with multiple passes), higher TOF analyser resolution and an enhanced dynamic range.

Novel Aspect
Use of high resolution, shape selective separations to characterise industrial formulations.

Options:

A post-doc is presenting author on this abstract? No
A graduate student is presenting author on this abstract? Yes
Research advisor's name Professor James Scrivens
Advisor's email j.scrivens@tees.ac.uk
An undergraduate student is presenting author on this abstract? No

Poster:

Ion Mobility: Applications

Submitting Author:

James Scrivens
Teesside University
Middlesbrough,
jim.scrivens@gmail.com