| Abstract Title: | Ion Mobility Separation Mass Spectrometry for simplifying complex MS/MS spectra to aid chemical characterisation. |
| Presenter Name: | Ms Caitlin Chapman |
| Co-authors: | Mr Callan Littlejohn Dr Meng Li Prof Peter O'Connor Dr Andrew D. Ray Dr Stephen W. Holman Dr Jackie A. Mosely |
| Company/Organisation: | National Horizon Centre, Teesside University |
| Country: | United Kingdom |
Abstract Information :
Ticagrelor is an antiplatelet medication manufactured by AstraZeneca for the treatment of acute coronary syndrome. It has a molecular weight of 522 u, and when subjected to tandem mass spectrometry analysis, it dissociates to give a very dense and complex spectrum, with numerous product ions having the same nominal m/z value. To fully characterise these product ions, it would be desirable to isolate each for further stages of MS/MS. The close proximity of the product ion peaks means this is not possible in most tandem mass spectrometers.
A traditional tandem mass spectrometry experiment would incorporate quadrupole isolation, and collision induced dissociation of the precursor ion. In experiments herein, ion mobility separation can be performed before quadrupole isolation (TIMS ToF MS, Bruker Daltonics Ltd.), or after the quadrupole (SELECT SERIES Cyclic IMS MS, Waters Corp.). A range of experiments have been devised using both instruments to see how well product ions within a nominal mass window can be further studied, aided by ion mobility.
Ticagrelor 1 mg/ml was directly infused at a rate of 10 ml/min. Electrospray ionisation was used to produce positive ions, with all operational parameters tuned to deliver the optimal peak intensity for [M+H]+ at m/z 523.
Initial focus on the product ion at m/z 363 shows there are 3 species within a 0.0351 mDa window (9.4T SolariX FT ICR MS, Bruker Daltonics Ltd.). This data was corroborated by the Cyclic IMS MS instrument but attempts to use the functionality of the Cyclic IMS MS to mobility isolate m/z 363 from the dense spectrum of product ions for further study proved too difficult to be definitive.
In-source dissociation was then used so that m/z 363 could be studied in more detail using the full capability of both IMS MS instruments. Using the Cyclic IMS MS, m/z 363 was isolated in the quadrupole prior to mobility separation. In this experiment multiple peaks were observed. Using the TIMS ToF MS, mobility separation was optimised for m/z 363 prior to the quadrupole, and multiple peaks were also observed. This data will be discussed in full and will demonstrate the extra depth of structural information provided by ion mobility, and the greater experimental capability ion mobility offers in the pursuit of understanding molecular ion fragmentation.
