ICP-MS is a powerful analytical technique that detects and quantifies trace elements by ionising a sample in an argon plasma and separating ions via a mass spectrometer. The process involves sample aerosol generation, ion extraction, ion beam focusing, mass filtering through a quadrupole, and detection by electron multiplication.
The theory and components of ICP-MS, including the nebuliser, spray chamber, torch, plasma, interface cones, ion optics, quadrupole mass analyser, and detector, are crucial for accurate elemental analysis.
The ICH Q3D guideline needs to be adhered to when testing for trace elements, which standardises the risk assessment and control of elemental impurities in drug products. This guideline applies to new and finished pharmaceuticals and classifies 24 elements based on toxicity and likelihood of occurrence into types 1, 2A, 2B, and 3.
The guideline outlines acceptable daily exposure (PDE) levels based on toxicity data and specifies evaluation through risk assessment, which includes identifying potential sources, measuring impurity levels, and deciding on control measures. Four assessment options (option 1, 2a, 2b, and 3) offer flexible paths depending on the formulation and daily dosage.
Why:
Client A required ICP-MS analysis to determine what was present within their sample to ensure compliance with ICH Q3D guidelines.
For whom:
This case study is designed for clients who are looking for elemental impurity testing in line with ICH Q3D
requirements.
How:
We conducted a risk assessment screening on three batches of the product, producing a semi-quantitative elemental “fingerprint” for over 50 elements. The results indicated that Lead was present, close to the permitted concentration limit set by guidelines, while no other concerning elements were detected.
Since no measures could be taken to reduce lead levels, it is now essential to test all future batches after manufacture to accurately quantify the lead content. A GMP validation was also completed for the product, quantifying Lead against the specified guidelines.
Outcome:
Client A now has a fully validated method that can be used to test each manufactured batch of their product, ensuring that Lead levels are below the required limits and that the product is safe for patient consumption.