If a sample is either an amine or its hydrochloride salt. What test can be done to determine if it's the salt form or not?

Definately wet chemistry methods are possible. Maybe some Beinstein based derivatization methods as well. Maybe just dissolve some and check solution pH (free amine pH 13? salt pH 5?). Any possibility to check free amino group and RNH3+ by FTIR? MS is not good doing that. Ion chromatography is cumbersome. Titration is an option. What about NMR? Any other ideas?

Thanks!

Assuming your sample consists only of the amine or hydrochloride salt, titration would work, though you would likely need an auto-titrator as the amine.HCl break is generally not sharp enough for a visual end point detection. If you add a known amount of standardized HCl to convert all the free amine to the HCl salt (add an excess of HCl), then perform a back titration with standardized KOH, you will get two potentiometric breaks. The first will be the excess HCl and the second will be for the amine.HCl. Simple calculations will allow you to determine the amount of free amine and amine.HCl in your original sample. You will also likely need to use a 10 to 20 % NaCl solution or 1:1 10 % NaCl:i-PrOH as your titration solvent to make the amine.HCl break more easily detected. Obviously any other acids or bases present in the sample may interfere with this method, though some organic acids can be detected as a separate break between the HCl and amine.HCl breaks.

Measure amount of chloride in your sample by titration or IC and recalculate the amount to amino acids. If you have one mole of chloride per mole of AA then you have a salt. If less than you have partial salt.