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

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.

MALDI mass spectrometry imaging as a complementary analytical method for improved skin distribution analysis of drug molecule and excipients.

In cutaneous drug delivery, it is widely accepted that the choice of excipients affects the delivery of a drug molecule to the skin. MALDI mass spectrometry imaging (MALDI-MSI) is an imaging technique which enables the simultaneous detection of multiple compounds. MALDI-MSI was applied to study the penetration of tofacitinib and excipients in porcine skin from two formulations with sodium lauryl sulphate (SLS) and dexpanthenol (DXP) using Franz diffusion cells. Further, the receptor media was collected for analysis of the permeated amounts of tofacitinib and excipients. The MALDI images showed DXP to be co-localized with tofacitinib in the epidermal and deep dermal region while SLS was distributed in the entire skin compartment. The permeation of tofacitinib for the two formulations was similar after 24 h, whereas, the percentage of permeated DXP was higher than for SLS. This study provided an overview of the skin penetration and permeation of drug molecule and excipients. MALDI-MSI showed differences in the DXP and SLS distribution. This indicates that the excipients interact with the skin through different mechanisms. Compound-specific imaging methods such as MALDI-MSI are potential tools to increase the understanding of the complex interplay between skin, excipients and the drug molecule for optimized cutaneous drug delivery.

Electrochemical simulation of phase I metabolism for 21 drugs using four different working electrodes in an automated screening setup with MS detection.

BACKGROUND: Electrochemical conversion of xenobiotics has been shown to mimic human phase I metabolism for a few compounds. MATERIALS & METHODS: Twenty-one compounds were analyzed with a semiautomated electrochemical setup and mass spectrometry detection. RESULTS: The system was able to mimic some metabolic pathways, such as oxygen gain, dealkylation and deiodination, but many of the expected and known metabolites were not produced. CONCLUSION: Electrochemical conversion is a useful approach for the preparative synthesis of some types of metabolites, but as a screening method for unknown phase I metabolites, the method is, in our opinion, inferior to incubation with human liver microsomes and in vivo experiments with laboratory animals, for example.