Chromatography Forum

Sorry, I was too quick to ask the last question. It is of course no problem to dilute my sample with water after the reaction has finished. The ester will be stable in a mildly basic aqeous solution - and the excess reagent is waste anyhow.

Here are some more ideas, depending on the specifics of your reaction:
1. Water can be removed from acetonitrile by azeotropic distillation. The mixture boils at a lower temperature than either component. For a small sample, you could simply evaporate to dryness, or near dryness if volatiles are important, and perhaps repeat as necessary. This is a longer process, but I have used it effectively on messy soil extracts. I do not know what the final water content is, though.

2. Water can be removed stoichiometrically with dimethoxypropane. It's cheap and readily available from Aldrich. In the presence of a trace acid catalyst, it reacts to form acetone and methanol. Again, I don't know how well this works at the ppm level, but it is easy and instantaneous. If your reagent can tolerate methanol and acetone, this is an easy solution.

Good luck. This is a difficult challenge, living in an aqueous world as we do! It would be easier off-planet!!

In preparative chromatography, we are handling this with a trick that we named "at-column dilution". For your problem, which is an analytical assay, it is a bit of work, and you need to juggle things around. Depending on the system(s) that you have it can be easy or very complicated.

Assume you run either an isocratic mobile phase or a gradient. You set up your injection port in a flow path that delivers 100% acetonitrile, while a second flow path delivers the rest of the isocratic or gradient composition. This way, the analyte is injected in 100% acetonitrile, and diluted just before the column to the (starting) composition of your mobile phase. This permits you to inject rather large injection volumes of an organic solvent without peak distortion.

It is work, and you need to decide if this is worth the effort.