By using a typical component in traditional Chinese medicine Pericarpium Arecae (PA), quantitative analysis of multi-components by single-marker (QAMS) was performed to determine the contents of four alkaloids. With a column packed with strong cation exchange bonded silica particles, the alkaloids were well separated, showing linear relationships within certain ranges. The limit of detection, limit of quantitation, precision, stability, repeatability and recovery all met requirements. By employing arecoline as internal standard, relative correction factors for arecaidine, guvacine and guvacoline at five concentrations were detected with three HPLC systems and three HPLC columns. The peaks of arecaidine, guvacine and guvacoline were positioned, during which the columns with the same packing materials from different manufacturers significantly affected relative retention values and retention time differences of the alkaloids. However, the columns, from different batches, managed to give relative retention values satisfying the requirements of HPLC peak positioning. The Thermo Fisher Scientific column packed with strong cation exchange bonded silica particles was finally selected by considering resolution and peak time. Compared with the external standard method, QAMS detected the alkaloid contents in 12 PA samples more accurately and reliably. The results provide valuable evidence for content determination and quality control of alkaloids in PA.