The aim of the present study was to develop a simple and sensitive LC-MS method for the estimation of delta8-tetrahydrocannabinol (delta8-THC) and its metabolite, 11-nor-delta8-tetrahydrocannabinol-9-carboxylic acid (11-nor-delta8-THC-9-COOH), in guinea pig plasma after topical drug application. The plasma samples were analyzed by LC-MS using negative-mode electrospray ionization detection and a simple liquid-liquid extraction technique. The mean recoveries for delta8-THC and its metabolite, 11-nor-delta8-THC-9-COOH, were 96.6 and 88.2%, respectively. The lower limits of quantification (LLOQ) for delta8-THC and 11-nor-delta8-THC-9-COOH were 3.97 and 7.26 nM, respectively. The topical treatment steady-state plasma concentrations of delta8-THC and 11-nor-delta8-THC-9-COOH were 8.24-27.63 and 19.66-23.17 nM, respectively, with a lag period of 0.3-2.2 h. This assay method is selective, sensitive, and reproducible for the determination of delta8-THC and 11-nor-delta8-THC-9-COOH at low concentrations in small volumes of plasma.