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

Autor: Christian Janfelt, Gitte Pommergaard Pedersen, Malcolm R. Clench, Anders Just Pedersen, Anne Mette Handler, Kim Troensegaard Nielsen
Rok vydání: 2021
Předmět:
Skin Cream
Pharmaceutical Science
Human skin
SOFTWARE
02 engineering and technology
030226 pharmacology & pharmacy
NORMALIZATION
0302 clinical medicine
Piperidines
MALDI-MSI
Skin
integumentary system
Chemistry
General Medicine
Middle Aged
Permeation
021001 nanoscience & nanotechnology
medicine.anatomical_structure
Drug delivery
Female
0210 nano-technology
Cutaneous drug delivery
Biotechnology
Adult
Drug Compounding
Skin Absorption
Administration
Cutaneous
Mass spectrometry imaging
Young Adult
03 medical and health sciences
Dermis
medicine
Humans
Distribution (pharmacology)
Skin permeation
In vitro release testing
Tofacitinib
Chromatography
Epidermis (botany)
HPLC-MS/MS
QUANTIFICATION
Skin penetration
Drug Liberation
Pyrimidines
TISSUE
Spectrometry
Mass
Matrix-Assisted Laser Desorption-Ionization
Feasibility Studies
Quantitative analysis (chemistry)
Zdroj: Handler, A M, Pedersen, G P, Nielsen, K T, Janfelt, C, Pedersen, A J & Clench, M R 2021, ' Quantitative MALDI mass spectrometry imaging for exploring cutaneous drug delivery of tofacitinib in human skin ', European Journal of Pharmaceutics and Biopharmaceutics, vol. 159, pp. 1-10 . https://doi.org/10.1016/j.ejpb.2020.12.008
ISSN: 0939-6411
DOI: 10.1016/j.ejpb.2020.12.008
Popis: 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.
Databáze: OpenAIRE
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