Objective To establish a method for the determination of metamizole sodium and chlorphenamine maleate in Zhongganling tablets. Methods The sample was determined by ion - pair HPLC after it was purified on Sep- Pak C18 microcolumn. The chromatographic conditions included: Hypersil DBS C18 chromatographic column(250mm × 4.6mm, i.d. 5μm) as an analytical column, methanolmixed solution of sodium heptanesulfonate and glacial acetic acid(600:400) as a mobile phase, the demetamizole sodium and chlorphenamine malcate were 99.6% (RSD was 2.1% and n was 6) and 98.0%(RSD was 1.5% and n was 6), respectively. Conclusion Metamizole sodium and chlorphenamine malcate can be determined respectively by HPLC with the same mobile phase when Sep - Pak C18 microcolumn solid- phase extraction method is used to substitute for the traditional sample pretreatment methods - refluxing, extracting and concentrating, and sodim heptanesulfonate ion - pair reagent in acid condition is selected.