I am trying to determine a method for one of the biphosphonates. Currently we are using indirect detection. This methodology seems successful at high concentrations, but at low concentrations (about 0.01mg/ml) the peak is too small to properly integrate. We are using an anion exchange column with very dilute nitric acid mobile phase with indirect UV detection. Can someone suggest a better more sensitive method that would work in my clients QC lab.

The answer to your question depends a bit upon the specific biphosphonates you have in mind. With postcolumn addition of ferric nitrate you can detect these compounds directly at 330 nm. A specific example is shown in Joachim Weiss' book: Ion Chromatography, second edition, published by VCH on page 134. In addition, some biphosphonates can be detected using direct conductivity detection with the use of a suppressor on the AS11 column. This method gives the best sensitivity. To advise on this I would need more information about the specific biphosphonates involved.