SLAS Discovery - Special Issue on Advances in MALDI Mass Spectrometry for Drug Discovery - Volume 22 Issue 10 - December 2017 - 1244

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that showed that brimonidine was detected in the retina by
15 min postdose.26 While three local routes of drug penetration have been described,19,20 a drug may reach the posterior
segment of the eye through a combination of routes. Using
IMS, we detected transcorneal distribution, presence in the
anterior chamber, and drug surrounding and in the posterior
region of the eye. This distribution of brimonidine suggests
that the uveal-scleral route is the main route of transit of
topically applied brimonidine. It is noted that the signal
observed around and in the back of the eye is low. This may
be due in part to the early time points used in this study,
which were likely before the peak concentration time (Tmax)
for brimonidine in the choroid/retina.18 Also, additional tissue sections through the depth of the eye may better capture
drug distribution in these structures. Inclusion of more time
points and more tissue sections may help better define drug
transit. Further, the low brimonidine signal may be due to
inadequate sensitivity needed to detect brimonidine in the
layers surrounding the eye. The current setup of MALDI
IMS used in our study had a spatial resolution of 80 µm.
With this limit, we were not able to differentiate between
sclera, choroid, or retinal tissue in the eye. Improvements to
the spatial resolution used in this study are needed to determine specifically which layers in the back of the eye contained brimonidine. Unique molecular localization in
different layers in the back of the eye has been demonstrated
in other studies by imaging at 10 µm on a commercially
available MALDI system.8
In summary, this MALDI imaging study showed that
brimonidine was detected in the cornea, anterior chamber,
and iris and reached the posterior segment of the eye. The
distribution of brimonidine suggests that the route of transit
following topical administration is mainly through the
uvea-scleral route, consistent with other reports.26 This
study demonstrates that IMS can be applied to monitor distribution and ocular transit of topically administered drug.
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 financial support for the research, authorship, and/or publication of this article.

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Table of Contents for the Digital Edition of SLAS Discovery - Special Issue on Advances in MALDI Mass Spectrometry for Drug Discovery - Volume 22 Issue 10 - December 2017
