Smokers’ mouth-level exposure to catechol, a potent co-carcinogen generated in the combustion of cigarette tobacco and transferred in the resulting mainstream cigarette smoke (MSS), was estimated via post-smoking, cigarette filter analysis of solanesol, an endogenous component of tobacco. The objectives of this study were to: (1) develop a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method to quantify catechol deliveries in MSS; (2) assess solanesol’s potential as a marker to estimate MSS catechol exposure by comparing the filter efficiencies of solanesol and catechol; and (3) establish calibration models from the correlation of measured solanesol cigarette filter levels with measured mainstream smoke catechol levels using commercial cigarettes. The results from a cigarette filtration study showed that the filter efficiencies of solanesol were proportional to that of catechol regardless the physical parameters of the filter. The relation between mainstream smoke delivery of catechol and filter solanesol was investigated, and a linear regression model was established for three popular United States cigarette brands. These established linear regression models could potentially be used to estimate the mouth-level intake of catechol in cigarette smoke.