|Abstract Number: ||920 - 2|
|Author Name: ||Iain David Grant Campuzano - Amgen|
|Session Title: ||ACS ANYL - Ion Mobility Spectrometry in Pharmaceutical Analysis|
|Event Type: ||Symposia|
|Event Title: ||Applications of Ion Mobility, Mass Spectrometry and Quantum Mechanics in Drug Discovery|
|Presider Name:||Alexander A Shvartsburg||Co-Author:||Paul Schnier|
|Date: ||Tuesday, March 19, 2013|
|Start Time: ||08:05 AM (Slot #2)|
|Ion mobility has the ability to rapidly separate isomeric species based on differences in their collision cross-sections ([omega]) in the gas-phase, as the ion moves through a neutral drift gas, typically He, under the influence of a weak electric field, thus providing specific information on ionic configuration. |
Since the introduction of traveling wave ion mobility (TWIM) technology in, application development has predominantly been protein structure based. Here we present the generation of a self-consistent set of [omega]N2 and [omega]He values for a group of drug-like molecules enabling calibration and accurate measurement of TWIM values, notably in N2 and comparison to an optimized N2 trajectory method algorithm. We also investigate the epimeric compounds betamethasone and dexamethasone, differing in chirality at a single carbon, resulting in a subtle, but detectable shape difference.
An alternative methodology to improve the separative properties of the TWIM device would be the use of more polarizable drift-gases. Herein we investigate the limits of peak-peak resolution improvements for the separation of shape-similar molecules, including structural isomers and analogues. We also demonstrate the use of molecular dynamics and quantum mechanics to analyse ionic electronic structure in conjunction with two trajectory method algorithms, as a means of understanding and explaining the observed TWIM separation in the different drift-gases.
Finally, we demonstrate the use of an in-house manufactured corona discharge probe, used in conjunction with both standard and nanoelectrospray, as an efficient and effective means of reducing an ion’s charge. This is demonstrated through reducing the effective charge of samples such as PEG 5K and 10K, glu-fibrinopeptide-b, lysozyme, alcohol dehydrogenase, pyruvate kinase, glutamate dehydrogenase, beta-galactosidase and GroEL. We also examine and discuss the resultant [omega]values of the charge-reduced ions.