Abstract

METHOD DEVELOPMENT AND VALIDATION FOR THE DETERMINATION OF ALUMINIUM AND SILICON IN ZOLEDRONIC ACID INJECTION BY INDUCTIVELY COUPLED PLASMA-MASS SPECTROMETRY (ICP-MS)

Shikha Chauhan* and Vishal Modi

ABSTRACT

Zoledronic acid, a potent bisphosphonate used in the treatment of bone-related disorders, requires stringent quality control to ensure patient safety. Trace elemental impurities such as aluminium (Al) and silicon (Si), potentially introduced during manufacturing or from contact materials, can pose toxicological risks. This study presents the development and validation of a sensitive and robust Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) method for the simultaneous determination of Al and Si in zoledronic acid injection (4 mg/5 mL). The method was optimized using appropriate internal standards, matrix matching, and collision/reaction cell technology to minimize interferences. Validation was performed in accordance with ICH Q2(R1) guidelines, evaluating parameters including linearity, precision, accuracy, specificity, limits of detection (LOD), limits of quantitation (LOQ), solution stability, and robustness. The method demonstrated excellent linearity (correlation coefficient ≥ 0.999), precision (RSD ≤ 2.66%), and accuracy (recovery 70–150%). LOD and LOQ values were suitable for trace-level analysis, and the method proved robust under varied conditions. The results confirm the method’s suitability for routine quality control and regulatory compliance in pharmaceutical analysis.

Keywords: Zoledronic acid, Aluminium, Silicon, ICP-MS, Method validation, Elemental impurities, Pharmaceutical analysis.