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

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/cm3) was found at the surface, while PG (384 mg/cm3) 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. The novel tailored multivariate curve resolution‐alternating least squares method is used to quantitatively determine the penetration profiles of caffeine (CF) and propylene glycol (PG) applied to the skin in a mixture. PG creates a reservoir at the superficial stratum corneum (SC) depth. The concentrations of CF and PG decrease monotonically and reach the detection limit at a depth of 60% SC depth (≈9 μm) and 80% SC depth (≈12 μm), respectively, indicating that neither permeate the SC.