Do not use a pH meter to adjust the pH of the mobile phase

hplc column imtakt yazawa shool mobile phase buffer preparation
When preparing the HPLC mobile phase, there may be a need to adjust the pH. In most cases, aren't we using a pH meter and adding acid or base until the desired pH is achieved?

Relying on a pH meter to prepare a "buffer" is fundamentally wrong. Because of the buffering action, the pH does not change easily even if the added amount is changed (that's why it's called a "buffering effect"). What's even more crucial for HPLC is the "ionic strength." With ion-exchange columns and separation systems that involve ionic interactions, insufficient ionic strength can affect peak shape and reproducibility of retention and separation.

The method of preparing the mobile phase based on the dependency of the pH meter, assuming "it's fine as long as the pH matches," is incorrect.
In biochemistry, when preparing a buffer, the correct method is to mix aqueous solutions of acid and base of the same concentration (50mM in this case) in a "volume ratio". With this, both ionic strength and pH can achieve reproducibility. Once you monitor the mixing ratio and pH for the first time, you can prepare quickly without needing a pH meter from the second time onward.

For "ammonium acetate" and "ammonium formate" and their buffers, which are essential for LC-MS, they excel in volatility, so even if they seem to be at a high concentration like 100mM, they mostly evaporate during ionization. The ionic strength is also one third of that of phosphoric acid. Because these organic salts are gentle on the column, the use of acetic or formic mobile phases as pH adjusters (buffers) is highly desirable.

WF26 / YAZAWA Itaru (