LEO Pharma A/S, Ballerup, Denmark; Department of Pharmacy, University of Copenhagen, Copenhagen, Denmark.
LEO Pharma A/S, Ballerup, Denmark.
Eur J Pharm Biopharm. 2021 Feb;159:1-10. doi: 10.1016/j.ejpb.2020.12.008. Epub 2020 Dec 25.
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.
在皮肤渗透研究中，对热分离的表皮和真皮提取物进行 HPLC-MS/MS 分析可估算穿透的药物量。在这项研究中，MALDI-MSI 可实现内源性分子和药物分子（托法替尼）的定性皮肤分布分析，以及表皮中托法替尼含量的定量分析。使用三种不同制剂（两种油包水乳膏 C1 和 C2 以及水凝胶）在 Franz 扩散细胞中研究了托法替尼向皮肤的传递。此外，进行了体外释放测试（IVRT），结果表明水凝胶中托法替尼的释放最快，C2 中的释放最慢。在体外皮肤渗透和渗透研究中，C1 显示出托法替尼在皮肤中的最大保留，而凝胶和 C2 则表现出较低的保留和较高的渗透。定量 MALDI-MSI 分析表明，C1 处理的样品中表皮中托法替尼的含量与 HPLC-MS/MS 分析相当，而 C2 和水凝胶处理的样品低于定量下限。该研究表明，MALDI-MSI 可用于定量测定表皮中的药物渗透，以及提供有关托法替尼定性皮肤分布的有价值信息。
