Applicability of total reflection X-ray fluorescence (TXRF) as a screening platform for pharmaceutical inorganic impurity analysis

Palladium (Pd) is extensively used in pharmaceutical small molecule drug substance processes, however it must be removed prior to release of the active pharmaceutical ingredient (API). Evaluation of four TXRF instruments and configurations were compared to ICP-MS instrumentation for trace metal analysis, most importantly for Pd. Standards and six pharmaceutical drug substances, triprolidine HCl, diphenhydramine HCl, chlorpheniramine maleate, pseudoephedrine HCl, ephedrine sulfate, and scopolamine HBr, were analyzed to determine linearity, sensitivity, accuracy, and precision for Pd plus Cr, Fe, Cu, Rh, and Pt versus interferences, particularly from Cl, S, and Ar, on the various X-ray fluorescence lines. Irrespective of instrument platform, in general X-ray sources capable of accessing Pd-K lines were found to be most effective in determination of Pd in APIs.

► TXRF achieves target parameters for metal testing in pharmaceuticals.
► TXRF enables utilization of limited sample amount for Pd testing.
► Determination of Pd by TXRF using Pd-K shell advantageous over Pd-L shell.
► Pd-K shell determination by TXRF driven due to interference of Cl.