The comparative verification of calibration curve and background fundamental parameter methods for impurity analysis in drug materials

Abstract

The United States Pharmacopeia (USP) has established general analysis guidelines of X‐Ray fluorescence (XRF) methodology in chapter <735>, XRF spectrometry. Meanwhile, the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH Q3D) guideline, presenting a policy for limiting 24 elements such as Cd, Pb, and As in drug products and pharmaceutical ingredients, has now reached Step 5 (Implementation). The limit values of ICH Q3D are strict, for example, near or less than 1 μg/g for Cd and Pb. Moreover, there are other difficulties for accurate analysis, such as different types of matrices and the very small sample volumes in the synthesis research process for new product development in the pharmaceutical industries. Energy dispersive XRF can correct the influence of various matrices and volumes and also has the advantages of nonchemical pretreatment and nondestructive analysis. Advancements in the quantitation by fundamental parameters (FP) method using theoretical calculations, background (BG)‐FP method, leads to reduction in the number of standard samples and effectiveness on the practical elemental impurity control in pharmaceutical researches and inspections. In order to show the applicability of using the BG‐FP method, in this study, the quantitative values of some hazardous inorganic impurities for Cd, Pb, As, V, Co, and Ni in a cellulose matrix were compared by calibration curve method and BG‐FP method through the verification of USP <735>. Both methods can meet the acceptance criteria for accuracy and precision in USP <735>. Copyright © 2017 John Wiley & Sons, Ltd.