Determination of (dichloromethylene)diphosphonate in physiological fluids by ion-exchange chromatography with phosphorus-selective detection

An analytical method is presented for the determination of (dichloromethylene)disphosphonate (Cl 2MDP) in serum and urine. Cl 2MDP is isolated from biological samples by adsorption onto precipitated calcium phosphate. Orthophosphate is separated from Cl 2MDP by anion-exchange chromatography using AG 1-X8 resin. Detection is accomplished on-line using a flame photometric detector. Potentially interfering condensed phosphates are removed by acid hydrolysis. Sample handling losses are corrected by monitoring the recovery of a [ 14C]Cl 2MDP spike added to the samples. Determinations of Cl 2MDP to concentrations as low as 2 μmol/l are possible. Extension of the method to determine other diphosphonates is discussed.