Quantification of 24 Inorganic Impurities in Vismodegib and Idelalisib Anti-Cancer Drug Substances by Using ICP-MS

Metal impurities in pharmaceutical products can originate from various sources, including manufacturing machinery, catalysts used during drug synthesis, and even the container-closure systems.

The objective of the present study is to accurately quantify trace levels of 24 metal impurities in the active pharmaceutical ingredients of the anticancer drugs vismodegib and idelalisib using an inductively coupled plasma mass spectrometer.

The diluent used in the analysis consists of a mixture of 3% nitric acid and 1% hydrochloric acid, while argon serves as the carrier gas. Helium is utilized as the collision gas at a flow rate of 4.3 mL/min. The plasma gas flow rate is maintained at 16 L/min, and the spray chamber temperature is controlled at 2.0 °C to ensure optimal stability during analysis. The dwell time for each metal impurity is set to 0.3 s, and the instrument is precisely tuned in helium mode to achieve accurate and interference-free detection of trace metal impurities.

No interference was observed from the calibration blanks, confirming the method's selectivity and accuracy. The sample recoveries were satisfactory, falling within the USP acceptance range of 70-150%.

The analytical procedure was performed in accordance with USP <233> and ICH Q3D(R2) guidelines, and all results were found to be within the established acceptance criteria, thereby validating the reliability and compliance of the method.

To date, no research studies have been reported on the determination of 24 elemental metal impurities in the drug substances vismodegib and idelalisib. Therefore, the present research aims to develop a unified and reliable analytical method for the quantification of these metal impurities in the active pharmaceutical ingredients of both drugs, ensuring compliance with regulatory standards and enhancing the overall quality and safety of the pharmaceutical products.