A high-performance liquid chromatographic method is presented for the analysis of the benzophenanthridine alkaloid, sanguinarine, found in plant extracts. The method is demonstrated to be applicable to analyzing samples such as saliva and gingival crevicular fluid for sanguinarine following a simple acidified methanolic extraction step. The method utilizes an ethyl silane column with acidic and basic ion-pairing reagents in the mobile phase with a limit of detection of 3 ng of sanguinarine in a sample.