Elemental Impurities for Hypertension Drug Product Injection by Inductively Coupled Plasma-Mass Spectrometry Using Validation and Development
Abstract
This study aimed to develop and validate a robust, sensitive, and accurate Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) method for the quantitative determination of elemental impurities in both the drug product and packaging materials of Hydralazine Hydrochloride for Injection, in compliance with ICH Q3D and USP <232>/<233> guidelines. The analysis was performed on a Thermo iCAP RQ ICP-MS system. The method optimized critical instrumental parameters, including dwell time (0.05 seconds), uptake time (60 seconds), wash time (20 seconds), and number of sweeps (30). An online internal standard mode was employed to correct for matrix effects and instrumental drift. The method was validated for system suitability, specificity, linearity, accuracy, precision, and sensitivity in accordance with international regulatory standards. The method demonstrated excellent linearity for all target elemental impurities, with correlation coefficients (r) of 1.000 across the established concentration ranges. Recovery studies yielded mean recoveries of 96% to 107%, confirming the method's accuracy. The precision, expressed as %RSD, was below 20% (n=9), well within the acceptance criteria set by regulatory guidelines. All validation parameters met the predefined acceptance criteria, confirming the method's reliability for its intended use. A comprehensive, fully validated ICP-MS method was successfully established for the routine quality control of elemental impurities in Hydralazine Hydrochloride for Injection. This study is the first to report a validated methodology specifically tailored to this parenteral formulation, addressing critical patient safety requirements and the increasing regulatory demands of the upcoming 2025 pharmacopoeial standards. The method's high sensitivity and multi-element detection capabilities make it a robust tool for ensuring the safety of pharmaceutical products.
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References
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