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 (Cl2MDP) in serum and urine. Cl2MDP is isolated from biological samples by adsorption onto precipitated calcium phosphate. Orthophosphate is separated from Cl2MDP 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] Cl2MDP spike added to the samples. Determinations of Cl2MDP to concentrations as low as 2 mumol/l are possible. Extension of the method to determine other diphosphonates is discussed.