Quantification of skin penetration of caffeine and propylene glycol applied topically in a mixture by tailored multivariate curve resolution‐alternating least squares of depth‐resolved Raman spectra

Abstract The quantitative determination of topically applied substances in the skin is severely limited and represents a challenging task. The porcine skin ex vivo was topically treated with a gel containing caffeine (CF) and propylene glycol (PG), and depth‐resolved Raman spectra were recorded with two confocal Raman microscopes. We applied a novel tailored multivariate curve resolution‐alternating least squares method to the selected spectral regions (512–604 and 778–1148 cm −1 ) of gel‐treated skin and quantitatively determined the concentrations of CF and PG in the stratum corneum (SC). The highest concentration of CF (181 mg/cm 3 ) was found at the surface, while PG (384 mg/cm 3 ) was found at 10% SC depth, indicating the formation of a reservoir at the superficial SC. The concentrations of CF and PG decreased monotonically and reached the detection limit at ≈60% and ≈80% SC depth, respectively, indicating that neither permeate the SC.