Is it possible to add basic additives to an acidic MP?

[Mike H.]

We currently are developing a RP separation where the main compound is a zwitterion but the impurities are not. Optimal tailing for the main component is ~pH 5.8, but optimal pH for the impurities is ~ 3.8. Does anyone know if it could be effective to add a competing base like DEA to an acidic MP of 3.8 and retain effectiveness? The phase is an endcapped C-18 solid core. thx

[Rndirk]

It will obviously raise the pH of the mobile phase. Sounds like you want to find a middle ground. You will need to test and see what happens, this is very hard if not impossible to predict...

[bunnahabhain]

You could try a pH gradient. Start with pH 3 and go up to 6.5, in the same time change the amount of acetonitrile (or whatever you use as organic modfier) according to the hydrophobicity of the individual analytes.
Or wait for a while, and Vlad Orlovsky will jump in and recommend a mixed-mode column

[aniket1706]

Try using ion pair reagents or can also try using different column chemistry like HILIC

[Vlad Orlovsky]

You might want to try mixed-mode approach. Usually gives much better retention and peak shape for ionizable analytes:
https://helixchrom.com/hplc-applications/

Contact me if you have questions.