Impurity Profiling And API Purification Via SFC

By Jennifer Lefler and Jacquelyn Cole

Synthetic routes for APIs (Active Pharmaceutical Ingredients) are becoming more complex, thereby demanding analytics to be more sensitive and sophisticated. Prior to toxicological or efficacy assays, compounds are scrutinized to identify, quantify and eliminate minute impurities. Analysis has gone beyond traditional chromatographic techniques, such as HPLC and GC, in order to resolve potential impurities through efforts that embrace diverse chemical environments. This concept is known as orthogonality. One such employable orthogonal technique is Supercritical Fluid Chromatography (SFC). SFC is considered a normal phase technique because it utilizes the relatively nonpolar, "liquid" carbon dioxide as the bulk of the mobile phase. Not only can temperature, flow rate, and composition/ polarity of this mobile phase be manipulated in order to resolve impurities, but the pressure of the system may also be employed to alter the internal chemistry of the technology. Furthermore, higher diffusivity of the mobile phase yields greater efficiency (smaller plate heights) resulting in more plates per unit height when compared to HPLC. End-users are constantly broadening the application of SFC to enhance their analytic arsenal.