Fiducial Markers for Distribution of Drug and Excipient on Tablet Surfaces by Multimodal Desorption Electrospray Ionization–Mass Spectrometry (DESI–MS) Imaging

Abstract

Fiducial markers are necessary for the accurate overlay of images obtained by different methods from small areas of a sample. Thus far, fiducial markers have been used for biological sample analysis by mass spectrometry imaging. In this work, spatial distributions of excipient and active drug substance at the surfaces of drug tablets produced under different pressures are observed by multimodal desorption electrospray ionization–mass spectrometry (DESI-MS) imaging with two novel fiducial marker systems being used to achieve accurate overlay of ion and optical images. DESI-MS ion images in the negative and positive ion modes as well as ion and optical images obtained from circa 3 mm² areas have been precisely superimposed, allowing observing the particulate composition of the tablet's ingredients, a feature that is remarkably conserved in spite of the pressure used to produce the tablet. This approach can be applied broadly for product development, quality control, and counterfeit detection.

[Supplementary materials are available for this article. Go to the publisher's online edition of Analytical Letters for the following free supplemental resource(s): Experimental details and supplementary Figures (S1-S4).]

Keywords:

• DESI imaging
• Drug tablet
• Mass spectrometry
• MS
• Multimodal analysis

Acknowledgments

The authors thank Drs. Tom Roper, Alireza Kord, and Choon Oh (GlaxoSmithKline) for critical review of the manuscript. Support from NSF 0852740-DBI is gratefully acknowledged.