Abstract: OBJECTIVE To find a suitale HPLC method to determine the related substances of repaglinide tablets recorded in Ch.P 2010. METHODS The performances of 4 kinds of HPLC which recorded in Ch.P 2010, USP 37 and EP 2014 were tested. The stability of mobile phase, ruggedness of the chromatographic column and detection sensitivity were comprehensively surveyed. RESULTS A large amount of crystals were precipitated in the mobile phase B of Ch.P 2010. Only one out of three chromatographic columns met the resolution requirement using EP 2014 method, which indicating the ruggedness of chromatographic column was poor in this method. In the method of USP 37 for repaglinide tablets, the retention time of the main impurity was too long and its peak became wider so that the detection sensitivity was reduced. The method of USP 37 for repaglinide had the advantages of mobile phase stability, excellent detection sensitivity and ruggedness of chromatographic column. CONCLUSION The method of Ch.p 2010 should be modified. The method of USP 37 for repaglinide is best fit the determination of the related substances is no more essential.