A simple high-performance liquid-electrospray ionization tandem mass spectrometric (HPLC-ESI-MS n ) method has been developed for the rapid identification of clindamycin and its related minor impurities in bulk drug. The ESI-MS n results obtained allowed us to propose plausible schemes for their fragmentations, which were confirmed further by electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICR-MS) using collision-induced dissociation (CID) method at high mass resolution. The positive ESI-MS/MS of clindamycin and its derivative compounds showed some diagnostic fragments, such as the neutral losses of H 2 O, HCl, methanethiol and 2-methylthio-ethenol, and the residue of 3-propyl-N-methylpyrrolidine and 3-ethyl-N-methylpyrrolidine, which are specific and useful for the identification of the lincosamide antibiotics and related impurities. According to the fragmentation mechanism of mass spectrometry and HPLC-UV-ESI-MS n data, six impurities of clindamycin have been identified on-line. Additionally, the positive ion mode extracted ion current (EIC) method has been used to separate and identify these lincosamide compounds.