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 bisphosphonates were in-line complexed by copper(II) ions and added to the acidic eluent, to yield an UV-absorbing complex. Chromatographic parameters 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 method was applied to the quality control of pamidronate injection concentrate and olpadronate tablets. The lower detection limit was 8 ng of disodium pamidronate, and the inter-assay precision was 1.0% for both pamidronate and olpadronate standard solutions and 1.8% for a 3 mg ml(-1) disodium pamidronate injection concentrate. The method was compared with a previously described ion-exchange chromatographic method with conductivity detection, without copper(II) ions in the eluent.