Evaluating topical product sensitivity and distribution using a multi-modal imaging approach

Session

Mass Spectrometry Imaging Across Length Scales in Life and Physical Sciences - Providing Atomic and Molecular Information

Authors

Jean-Lu Voorng (1), D. Tsikritsis (1), P. Zarmpi (2), V. Tyagi (1), A. Dexter (1), N.A. Belsey (1), R.H. Guy (2)

Affiliations

1. National Physical Laboratory
2. University of Bath, Department of Pharmacy & Pharmacology

Keywords

Abstract text

There is a need to characterise non-invasively both the epidermal bioavailability of a topically applied drug and to distinguish correctly between formulations that are bioequivalent, i.e., to measure if a generic formulation performs the same as the branded product. In this study, Time-of-Flight Secondary Ion Mass Spectrometry (TOF-SIMS) was used to detect, characterise, and image the distribution of 4-cyanophenol a drug permeation enhancer(1) within a pig skin tissue homogenate and pig skin tissue sections(2). 

Due to its high sensitivity and the capability to provide chemical mapping of the sample, SIMS enables a step-by-step approach to the problem starting from the screening of the product to investigating the limit of detection within a biological matrix. In this study, we have investigated the distribution of 4-cyanophenol in skin using a multi-modal imaging approach. Correlative mass spectrometry imaging (MSI) measurements with non-invasive Raman spectroscopy on the same sample provides superior chemical specificity and permits the distribution of the compound to be accurately characterised using spatial registration(3). Finally the OrbiSIMS has been used to investigate the contribution of endogenous species that might interfere with the signal of interest in TOF-SIMS(4) 

In this work, the compound of interest has been successfully detected as an intact molecular ion and a linear response of intensity as a function of concentration has been obtained. Finally, the distribution 4-cyanophenol within a pig skin tissue section was mapped and a strong correlation between SIMS and Raman spectroscopy was demonstrated.

References

References

1. Romonchuk et Al. Skin Pharmacol Physiol, 23(3), 2010, 152–163
2. Summerfield et al. Molecular Immunology 66 2015, 14–21
3. Siy, P. W.et al. BioInformatics and BioEngineering. 2008, BIBE. 2008, 8th IEEE International Conference on, IEEE: 2008; pp 1-6
4. Passarelli et al. Anal. Chem. 2015, 87, 6696-6702