ION-EXCHANGE LIQUID-CHROMATOGRAPHIC ANALYSIS OF BISPHOSPHONATES IN PHARMACEUTICAL PREPARATIONS

A simple, fast and uniform method has been developed for the quantitat ive determination of bisphosphonates in the quality control of pharmac eutical preparations. The method is based on ion-exchange liquid chrom atography with conductivity detection. Separation is performed on a Wa ters IC-PAK Anion column using 2 mM nitric acid or 25 mM succinic acid as the mobile phase. Retention of the bisphosphonates can be influenc ed by pH and the anion concentration of the mobile phase. Sensitivity and selectivity are sufficient for the assay of bisphosphonates in bul k drug and pharmaceutical preparations. Sample preparation comprises d issolution or dilution of the sample in the mobile phase followed, if necessary, by filtration prior to HPLC analysis. Since the method is s tability indicating, it is also well suited for shelf-life studies of bisphosphonate pharmaceutical preparations. Validation of the analytic al method for the assay of pamidronate injection indicated an intra-da y reproducibility of 1.7% (n = 6) and an inter-day reproducibility of 2.7% (n = 6). A linear relationship between response and concentration was found in the concentration range studied from 200 ng to 10 mug pa midronate per 20 mul injected. The lower limit of detection (signal-to -noise ratio = 3) of pamidronate was about 100 ng.