Application of LC-Direct-EI-MS in in vitro dermal absorption study: quantitative determination of trans-cinnamaldehyde

We propose a new analytical approach, based on liquid chromatography (LC) coupled to electron ionization mass spectrometry (EI-MS), using a Direct-EI interface, for dermal absorption evaluation studies. Penetration through the skin of a given compound is evaluated by means of in vitro assays using diffusion cells. Currently, the most popular approach for the analysis of skin and fluid samples is LC coupled to electrospray ionization tandem mass spectrometry (ESI-MS/MS). However, this technique is largely affected by sample matrix interferences that heavily affect quantitative evaluation. LC-Direct-EI-MS is not affected by matrix interference and produces accurate quantitative data in a wide range of concentrations. Trans-cinnamaldehyde was chosen as test substance and applied in a suitable dosing vehicle on dermatomed human skin sections. This compound was then quantified in aliquots of receptor solution, skin extract, cell wash, skin wash, carbon filter extract, cotton swab extract, and tape strip digest. On column limits of detection (LOD) and limits of quantitation (LOQ) of 0.1 and 0.5 ng/μL, respectively, were achieved. Calibration showed satisfactory linearity and precision for the concentration range of interest. Matrix effects (ME) were evaluated for all sample types, demonstrating the absence of both signal enhancement and signal suppression. The Direct-EI absorption profile was compared with that obtained with liquid scintillation counting (LSC), a recognized ME free approach. A good correlation was found with all samples and for the overall recovery of the dosed substance.