Abstract: A method for the simultaneous determination of alendronate, pamidronate, ibandronate and risedronate using ion chromatography with integrated pulsed amperometric detection (IPAD) has been developed. The electrochemical behavior showed the catalytic currents of these bisphosphonates are based on the oxidation of amines in their structures. Because the bisphosphonates are polar compounds and present as anions under alkaline condition, therefore, they can be separated by anion exchange chromatography. A Dionex AS18 column (250 mm×2 mm) and an AG18 column (50 mm×2 mm) and 24 mmol/L NaOH solution were used for the separation. Multi-step potential waveform parameters were optimized to maximize the signal-to-noise ratio (S/N), which exhibited adsorption/desorption catalytic features at the gold electrode surface in alkaline solution. Utilizing the optimized waveform, the method showed good linearity (r2=0.9972~0.9995), satisfactory repeatability (relative standard deviations (RSDs) of the peak areas in the range of 0.84%~1.37%) and sufficient sensitivity (limits of detection of 0.061~0.18 μg/mL) for the identification of the four bisphosphonates. The recoveries were 80.81%~97.32% with the RSDs of 1.46%~3.02%. It is demonstrated that this method is a rapid and simple one for the determination of the four bisphosphonates in human plasma.

Key words: alendronate, integrated pulsed amperometric detection (IPAD), pamidronate&mu, ibandronate&mu, ion chromatography (IC), plasma, risedronate&mu