Ion‑pair reagents are frequently used in traditional reversed‑phase (RP) HPLC to increase the retention of poorly retained analytes or to improve peak shape caused by silanolic tailing.

However, in LC‑MS these additives often introduce serious ion suppression, reduced sensitivity, increased contamination, and difficult system cleanup.

Fortunately, when using Cogent TYPE‑C™ silica hydride columns, ion‑pair agents are typically unnecessary because the columns themselves provide the required retention and selectivity without compromising MS performance. 

Why TYPE‑C™ Columns Reduce or Eliminate the Need for Ion‑Pair Agents

The surface of a TYPE‑C silica hydride column contains very few silanol groups, dramatically reducing the traditional causes of peak tailing. Reduced silanol activity eliminates the need for ion‑pair agents that are typically used to mask these interactions in RP mode.

Furthermore, TYPE‑C columns uniquely support Aqueous Normal Phase (ANP), a mechanism that naturally provides strong retention for polar and charged compounds—including both small molecules (<100 Da) and larger analytes such as peptides—without the need for ion‑pairing chemistry. 

How ANP Avoids Ion Suppression in LC‑MS

Because ANP functions effectively with low‑concentration volatile additives, it is inherently more compatible with LC‑MS. Typical ANP mobile phases use:

• Formic acid
• Acetic acid
• Ammonium acetate
• Ammonium formate

All are recommended at ≤10 mM, ensuring they remain MS‑friendly and do not cause ion suppression problems. This allows the analyst to retain and separate charged or highly polar compounds without introducing the high‑concentration non‑volatile salts associated with traditional ion‑pairing.

Who Benefits Most from This Approach?

Scientists working with:

• Charged analytes (positive or negative) with molecular weights below 100 Da
• Peptides and small biomolecules
• Polar uncharged compounds

These analyte classes routinely exhibit strong, stable retention in ANP mode without ion‑pair agents, allowing for clean MS detection and long‑term instrument stability.

Summary of Advantages When Using TYPE‑C Columns Instead of Ion‑Pairing

• Eliminates common LC‑MS ion suppression pathways
• Avoids column fouling associated with ion‑pair reagent adsorption
• Maintains excellent peak shape due to low silanol activity
• Provides strong ANP retention for polar compounds
• Uses only low‑level volatile additives (≤10 mM) suitable for MS detection