Application of X-ray fluorescence spectrometry for screening pharmaceutical products for Elemental Impurities according to ICH guideline Q3D

Abstract

Energy-dispersive X-ray fluorescence spectrometry (EDXRF) is a suitable analytical procedure for screening drug products for Elemental Impurities (EI) according to ICH guideline Q3D. EDXRF represents a cost-efficient, robust and standard-free alternative compared to other methodologies for trace analysis, and therefore utilization of this application should be encouraged. This study demonstrates the capability of EDXRF for EI screening of oral solid dosage drug products (OSD products) within a defined matrix range. Method development and validation focused on class 1 (Cd, Pb, As, Hg) and class 2A (Co, V, Ni) elements, as defined by ICH guideline Q3D. In order to limit validation activities, a novel cluster approach was applied, based on matrix properties. This included comprehensive characterization of method performance parameters for exemplary pharmaceutical matrices and demonstration of LOQ independence from matrix effects by using a set of limit samples representing typical matrix variations of OSD products. The methodology can be used as a limit test for class 1 and class 2A elements and is fully compliant with method validation requirements according to the European Pharmacopeia. The novelty of the present work is the application of EDXRF for a routine screening of OSD products for Elemental Impurities within the pharmaceutical industry beyond previously published feasibility studies for a limited number of pharmaceutical raw materials or products.

Keywords: EDXRF; Elemental impurities; ICH Q3D; ICH guideline Q3D; Pharmaceutical products; X-ray fluorescence.