SLAS Discovery - Special Issue on Advances in MALDI Mass Spectrometry for Drug Discovery - Volume 22 Issue 10 - December 2017 - 1269

1269

Chandler et al.
acetylcholine as the analyte only. Analyte-dependent variations in the TIC of the signal detected are to be expected.
Consequently, individual investigations for a specific analyte
of interest, in its deconstructed assay conditions, should be performed prior to full screening assay development to determine
the highest buffer concentrations that deliver an optimal intensity for the analyte in question. In addition, the accumulative
effect of all the selected assay components and the reaction
kinetics should in all instances be evaluated under the
MS-friendly buffer conditions to determine if the biology/
pharmacology is affected.
By adopting this reevaluation of the buffers and other
assay components incorporated into screening assays, to
eliminate the concerns involving ion suppression effects,
screening by MALDI-MS has the potential to provide a
label-free, direct-detection alternative to the fluorescence
and chemiluminescence approaches traditionally used. This
report goes some way into defining the optimal conditions
for compatibility of the most widely used screening assay
base buffers, additional components, detergents, cell culture
media, and other additives within screening by MALDI-MS.
As a result, a balance between limiting the ion suppression
effects on the analyte ion signal intensity and the degree of
requirement for a particular assay component condition
needs to be assessed prior to all MALDI-MS assay constructions. Furthermore, continued evaluation and the addition of other assay components need to be encouraged to
generate a complete catalogue of favorable buffers and their
suitable concentrations for use in MALDI-MS screening to
ensure full success of the technique.
Acknowledgments
We thank Meike Hamester, Jens Fuchser, Arne Fuetterer, Arndt
Asperger, Volker Sauerland, Dagmar Niemeyer, Rainer Paape, Anja
Resemann, Markus Kayser, Matthias Koethe, Sergei Dikler, Jens
Hoehndorf, and Juergen Srega from Bruker Daltonics (Bremen,
Germany) for their input and valuable discussions. We also thank
Robert Hughes from GSK, Stevenage, for his technical advice in

setting up the Agilent Bravo Automated Liquid Handling Platform
384-well plate dilutions.

Declaration of Conflicting Interests
The authors declared no potential conflicts of interest with respect
to the research, authorship, and/or publication of this article.

Funding
The authors received no funding for this work. All research was
completed as work-for-hire for the employer GSK.

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