Question of the month: March 2020

My active pharmaceutical ingredient (API) is present in the hydrochloride form.

Does that mean I can only use impurity reference standards which are also in the hydrochloride form?

Quite simply: no! Based on our own experience and that of our customers, it does not appear to matter in what salt – or even free base – form your impurity reference standards are present. 

If an API is present as an HCl salt, the impurities in it might be present as an HCl salt or a free base, maybe even as another salt. No matter which, in HPLC the mobile phase determines in what solvated form each impurity passes the column/detector, meaning retention time, UV spectrum, and also mass spectrum will be similar regardless of the form in which the impurity is present in the tested API sample. 

Therefore it also doesn’t matter in what form your impurity reference standard is present. But, of course, you do need to know exactly which form this is, particularly if you want to quantify with that impurity standard.