Chromatography Forum

Dear,

I would like to know if someone works in the development of LC-MS methods to analyze alendronate.
I use ion-chromatography and formate buffer 16 mM pH 4.5 as mobile phase.
I have a problem concerned about this analyte: in the range from 1 to 30 ppm the method is not linear and I can not work with lower concentrations because sensitivity is too poor.
What can I do to solve this problem?

I have a few thoughts on sensitivity.

If you are using positive ionization, try optimizing in negative and see if sensitivity improves.

If you do not have any organic solvent in your mobile phase, try including some (~ 5 to 10% methanol or ACN), unless it will mess up your chromatography or damage your column.

If you can't use any organic solvent with this chromatographic method, consider trying to chromatograph this compound using HILIC. You can search this board (or the internet) and find lots of info on HILIC (hydrophilic interaction chromatography).

I am using negative ionization and I will try to add a small quantity of an organic solvent.
The problem is related to linearity that is too poor. I do not know if the problem is the high concentration of the analyte I am using (20 ppm), but I can not decrease concentration because sensitivity is not good.

One possible explanation of your linearity problem is related to the fact that your analyte is a potent chelating agent. Are you observing an extreme drop-off in signal at low concentrations? If so, trace metals in your analytical system might be the culprit. Try injecting a healthy concentration of EDTA prior to one of your low standards to see if this affects response at low concentrations. If so, you might do well to a chelating agent to your mobile phase or a chelating trap column ahead of the injection valve.