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Analytical Chemistry

Method Maps Chemicals As They Migrate Into Skin

Drug Delivery: Mass spectrometry technique could help studies of transdermal compounds

by Elizabeth K. Wilson
April 25, 2014 | A version of this story appeared in Volume 92, Issue 17

A mass spectrometry technique gaining popularity for medical applications such as imaging tumor surfaces can also be used to study the migration of small-molecule compounds applied to the skin (J. Am. Chem. Soc. 2014, DOI: 10.1021/ja501635u).

Because skin is such a complex organ, the method could be a boon for researchers developing transdermal drugs.

Stanford University chemistry professors Richard N. Zare and Justin Du Bois, postdoc Livia S. Eberlin, graduate student John V. Mulcahy, and colleagues show that desorption electrospray ionization-mass spectrometry (DESI-MS) imaging has numerous advantages over other methods that require complicated preparation of skin samples.

What’s more, DESI-MS imaging can be performed under ambient conditions, instead of in a vacuum environment, as other MS methods require. In addition, test compounds don’t have to be radioactively labeled or tagged with cumbersome dye molecules that could affect the compounds’ normal migration through skin.

“That’s why this method is very appealing,” says Mark R. Prausnitz, a chemical and biomolecular engineering professor who heads the Laboratory for Drug Delivery at Georgia Tech.

DESI-MS was developed a decade ago and involves spraying charged solvent droplets at a surface. Backsplash droplets containing dissolved molecules are then captured and analyzed using a mass spectrometer. The method has been used for medical applications such as imaging drugs in tissue samples.

The Stanford group selected a number of small molecules that alter sodium channels in skin cells, including lidocaine and a shellfish toxin. They applied them to the surface of skin samples and were able to track the compounds’ migration to a depth of 1.2 mm.

Such investigations of drug migration are needed to expand the limited repertoire of transdermal drugs, Prausnitz says. Only about 30 drugs, such as nicotine, have transdermal versions. The drugs must be small, lipophilic, and effective at a low dose.

With this newly adapted tool, however, scientists could more readily study methods to enhance skin permeation, Prausnitz says. “We’re very interested in the pathway—which part of the skin did the drug go through?”

Credit: J. Am. Chem. Soc.
This DESI-MS image shows the percentage of penetration of lidocaine on a skin sample (red = 100%).
Mass spectrometry image of a skin sample.
Credit: J. Am. Chem. Soc.
This DESI-MS image shows the percentage of penetration of lidocaine on a skin sample (red = 100%).


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