Quantitative MALDI mass spectrometry imaging for exploring cutaneous drug delivery of tofacitinib in human skin

HANDLER, Anne Mette, POMMERGAARD PEDERSEN, Gitte, TROENSEGAARD NIELSEN, Kim, JANFELT, Christian, JUST PEDERSEN, Anders and CLENCH, Malcolm (2020). Quantitative MALDI mass spectrometry imaging for exploring cutaneous drug delivery of tofacitinib in human skin. European Journal of Pharmaceutics and Biopharmaceutics, 159, 1-10.

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Official URL: https://www.sciencedirect.com/science/article/pii/...
Link to published version:: https://doi.org/10.1016/j.ejpb.2020.12.008
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    Abstract

    In skin penetration studies, HPLC-MS/MS analysis on extracts of heat-separated epidermis and dermis provides an estimate of the amount of drug penetrated. In this study, MALDI-MSI enabled qualitative skin distribution analysis of endogenous molecules and the drug molecule, tofacitinib and quantitative analysis of the amount of tofacitinib in the epidermis. The delivery of tofacitinib to the skin was investigated in a Franz diffusion cell using three different formulations (two oil-in-water creams, C1 and C2 and an aqueous gel). Further, in vitro release testing (IVRT) was performed and resulted in the fastest release of tofacitinib from the aqueous gel and the lowest from C2. In the ex vivo skin penetration and permeation study, C1 showed the largest skin retention of tofacitinib, whereas, lower retention and higher permeation were observed for the gel and C2. The quantitative MALDI-MSI analysis showed that the content of tofacitinib in the epidermis for the C1 treated samples was comparable to HPLC-MS/MS analysis, whereas, the samples treated with C2 and the aqueous gel were below LOQ. The study demonstrates that MALDI-MSI can be used for the quantitative determination of drug penetration in epidermis, as well as, to provide valuable information on qualitative skin distribution of tofacitinib.

    Item Type: Article
    Additional Information: ** Article version: AM ** Embargo end date: 25-12-2021 ** From Elsevier via Jisc Publications Router ** Licence for AM version of this article starting on 25-12-2021: http://creativecommons.org/licenses/by-nc-nd/4.0/ **Journal IDs: issn 09396411 **History: issue date 28-02-2021; published_online 25-12-2020; accepted 11-12-2020
    Identification Number: https://doi.org/10.1016/j.ejpb.2020.12.008
    Page Range: 1-10
    SWORD Depositor: Colin Knott
    Depositing User: Colin Knott
    Date Deposited: 05 Jan 2021 11:07
    Last Modified: 05 Jan 2021 11:07
    URI: http://shura.shu.ac.uk/id/eprint/27882

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