Data Independent and Data Dependent Acquisition Strategies Combined With Ion Mobility for Drug Metabolism and Pharmacokinetics

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Caitlyn Da Costa, Jayne Kirk, Russell Mortishire-Smith, Sherri Naughton and Mark Wrona
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Data independent strategies for complex mixture analysis, particularly within a higher throughput pharmaceutical environment offer significant efficiency advantages in that they enable a generic, non-biased strategy for data acquisition, suitable for compound identification. The poster will discuss data-independent-acquisition strategies such as full scan low and high collision energy acquisition in ion-mobility enhanced variant (HDMSE) for use in DMPK applications.

Data dependent strategies remain an important tool in the MS toolbox for when MS/MS spectra through quadrupole mass selection is required. The acquisition mode Product Ion Confirmation (PICs) will also be discussed, as this affords, within one acquisition, low energy, high energy and HS MS/MS spectra reducing the need for repeat injections. Quadrupole mass selection affords greater selectivity leading to more definitive MS/MS spectra.

A large number of closely eluting metabiolites including hydroxylations, di hydroxylations and various glucuronidated species were accurately resolved, measured by m/z and CCS (to less than 3 ppm and 2 % CCS accuracy) and clean product ion spectra obtained by both techniques. Whilst HDMSE implementation enables greater dynamic range and routine extrapolation of CCS values for parent and metabolites, data dependent modes can be necessary for more targeted applcaitions. Acquisition modes, the utility of HD (ion-mobility enhancement) and quality of data between the modes will be discussed in addition to the practicality of having these available to DMPK researchers.

Two commercially available drugs, nefazodone and buspirone were incubated in hepatocytes at 10 µM substrate concentration and samples prepared for analysis by protein precipitation. Aliquots of each sample set were spiked into human urine at a ratio of 1:10. HDMSE, Product Ion Confirmation (PICS), IMS-enabled DDA data sets were acquired on a VION IMS-QTof mass spectrometers. Data were acquired and processed using UNIFI, a workflow driven informatics platform, for effective and efficient data interogation and reporting.

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