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Aiming at the development of strategies to prevent the hand-foot-syndrome, we propose evaluation of the amount of chemotherapeutics in the human skin together with carotenoids the latter serving as marker substances for the dermal antioxidative status. This approach is demonstrated in applying two-color Raman spectroscopy for selective detection of chemotherapeutics and carotenoids, due to excitation at 785 and 532 nm, respectively. Porcine ear skin has proven to be suited as a model for corresponding spectroscopic basic in vitro investigations.