I am working on a method to detect galacturonic acid with ES or APCI detection. My column requires acidic mobile phase but I want to do negative ion detection. I am attempting to add ammonia post-column but I am getting far less signal than without post-column. Does anyone have experience with this kind of situation? Is my salt content too high? My mobile phase is 0.1% (17 mM) acetic acid and I was adding 28 mM NH4OH post-column.

Is it possible that you are diluting your sample too much? What is the flow rate of your LC and of the post-column pump? Is 28mM the concentration of the ammonium hydroxide you are adding, or the concentration after the mixing?

Surprisingly, ESI and APCI negative will often work well with acidic eluents, as long as you aren't using TFA. I've run lots of analyses with 0.1% acetic acid in the mobile phase, and find that post-column addition is almost never necessary.

Thanks for the reply.
I was adding equal (0.6 ml/min) or less flow rate in the post-column, so I was diluting no more than 1:1.
I was gettting roughly a 200 pg detection limit with ES, but wanted to see if I could boost it any more than that.

Try increasing the concentration of your post-column base by a factor of 10, and decreasing its flow rate by a factor of 10. This way, you are adding the same amount of ammonia but diluting your sample much less. If your final buffer concentration is 28mM NH4OH + 17mM acetic acid, that does not seem too high

In addition, I recommend that you use a knitted open tubular (KOT) reactor for effcient mixing. At this flow rate a 0.25 mm ID KOT will give you very good mixing, essentially without any additional bandbroadening.
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