HIGH-PERFORMANCE ION-EXCHANGE CHROMATOGRAPHY WITH IN-LINE COMPLEXATION OF BISPHOSPHONATES AND THEIR QUALITY-CONTROL IN PHARMACEUTICAL PREPARATIONS

An ion-exchange chromatographic method using an anion-exchange column was developed for the analysis of a number of bisphosphonates. The bis phosphonates were in-line complexed by copper(II) ions and added to th e acidic eluent, to yield an UV-absorbing complex. Chromatographic par ameters were studied for eight different bisphosphonates, particularly amino-1-hydroxyalkyl-1,1-bisphosphonates; special attention was paid to the relationship between retention and complex formation. The metho d was applied to the quality control of pamidronate injection concentr ate and olpadronate tablets. The lower detection limit was 8 ng of dis odium pamidronate, and the inter-assay precision was 1.0% for both pam idronate and olpadronate standard solutions and 1.8% for a 3 mg ml(-1) disodium pamidronate injection concentrate. The method was compared w ith a previously described ion-exchange chromatographic method with co nductivity detection, without copper(II) ions in the eluent.