Why Use Ammonium Acetate in ANP and LC‑MS? – Technical Guidance

Ammonium acetate is one of the most versatile and widely used mobile‑phase additives for Aqueous Normal Phase (ANP) and LC‑MS methods because it provides a near‑neutral pH environment while maintaining excellent volatility and compatibility with mass spectrometers.

When added to ANP methods, ammonium acetate helps keep many organic acids ionized, which improves overall retention, peak shape, and reproducibility for polar analytes. This makes it a preferred choice over phosphate buffers, which provide similar pH control but are not compatible with LC‑MS due to their non‑volatile nature. 

In ANP workflows—especially on silica‑hydride–based stationary phases like Cogent TYPE‑C™ columns—ammonium acetate not only supports the ionization state of analytes but also enhances the formation of the charged surface species essential to ANP retention behavior.

However, technical users should be aware that ammonium acetate can adsorb strongly to silica‑based stationary phases, altering the surface environment and retention characteristics over time. For this reason, once ammonium acetate is introduced to a particular column, that column should be dedicated to methods using ammonium acetate to maintain consistent chromatographic behavior and eliminate cross‑method contamination or unexpected shifts in selectivity.

This property makes ammonium acetate an excellent tool when developing dedicated ANP or LC‑MS methods where control over analyte ionization and mobile‑phase pH is essential—but it means users must plan their method portfolios to avoid mixing ammonium acetate methods with incompatible workflows on the same hardware.