Trace and risk level determination procedure for carcinogenic and genotoxic inorganic catalysts and environmental contaminants from the medicinal manufacturing components and packaging materials by using ICP-MS

Abstract

The objective of the current study is to formulate an accurate and linear analytical method to precisely estimate the trace level carcinogenic, genotoxic and environmental hazardous metal impurities present in pharmaceutical manufacturing components and packaging materials via inductively coupled plasma mass spectrometer (ICPMS) and using thiourea complexing agent. The thiourea first forms complex with the metal ions and readily pulls out the metal impurities when the sample is extracted in a microwave pressure digestion system. Moreover, thiourea is able to simplify the sample preparation, reduce the time and cost for determination of the trace level toxic metal impurities present in pharmaceutical manufacturing components and packaging materials. Argon is utilized as carrier gas. Helium is used as a collision gas with a flow rate of 4.3 mL/minute. The plasma gas flow rate is set to 18 l/minute, the spray chamber temperature is adjusted to 2.0°C, and metal impurities dwell time is 0.3 seconds. The current method was validated against USP< 233 > and ICH Q3D(R1) guidelines. The sample recoveries were found to be USP< 233 >limit of 70 %-150 %. The high accuracy, robustness and sample recoveries validate the method to accurate estimation of trace level toxic elemental impurities present in manufacturing components and pharmaceutical packaging materials.