Menstrual hygiene products (MHPs) like tampons, sanitary towels and panty liners are widely used by women and come in close contact with the intimate parts of the human body, which consist of mucosae that lack the important barrier function of normal skin. Hence, substances leaching from MHP can easily penetrate and become systemically available. This study aims to develop a new in chemico methodology that allows to identify and measure realistic consumer exposure levels of several skin sensitizers and irritants leaching from MHPs under simulated use conditions. To assess the leaching of chemicals from MHPs, a menstrual fluid simulant (MFS) simulating pH, osmolarity and protein binding was first established. Subsequently, an analytical methodology was developed for nine well-known skin sensitizers and skin irritants. In short, the MFS samples underwent salting-out assisted liquid-liquid extraction before ultra-high performance liquid chromatography coupled with a triple-quadrupole mass spectrometry analysis. Validation was performed according to the total error approach with acceptability limits of ±15% regarding the total analytical error (including systematic and random bias). Fifteen commercially available MHPs were assessed. Six products were found to leach at least one of the following five sensitizing and irritating compounds: α-isomethyl ionone, benzyl salicylate, hexyl cinnamaldehyde, linalool and piperonal. Piperonal was the most abundant compound leaching from the MHPs, with leaching concentration levels measured to 28.22 μg/g. In addition, the leaching level of benzyl salicylate was found to be 11.03 μg/g. The latter fragrance concentration is above 10 μg/g and would trigger mandatory labelling if the Cosmetic Regulation would apply for MHPs. However, none of the identified and quantified skin sensitizers were mentioned on the packaging. In conclusion, this novel methodology makes it possible to estimate realistic human exposure levels to skin sensitizers and irritants through the use of MHPs. Availability of these exposure estimates is vital to carry out a quantitative health risk assessment of these substances.