ICH Q3D based elemental impurities study in liquid pharmaceutical dosage form with high daily intake - comparative...

Guideline for Elemental Impurities-Q3D of the International Conference on Harmonisation represents a new paradigm in the control of elemental impurities (EIs) in pharmaceuticals. It changes the approach toward control of EIs from the historical 'heavy metals test', to a scientific-based risk assessment and testing by modern analytical instrumentation such as inductively coupled plasma-optical emission spectroscopy (ICP-OES) and inductively coupled plasma-mass spectrometry (ICP-MS). Management of EIs related to all finished drug products must be implemented in strict compliance with the regulatory requirements of pharmaceutical industry due to their quality and safety concerns. Testing for presence of EIs from Class 1 and Class 2a in methadone hydrochloride 1 mg/ml oral solution with recommended daily intake of 150 mg methadone hydrochloride was initially performed on ICP-OES using in-house validated method according to the requirements of pharmacopoeias, in line with Q3D. During the procedure, it became apparent that ICP-OES has its own limitations, especially when it comes to testing arsenic and lead in low concentrations. ICP-MS in-house validated method was developed and employed for determination of trace concentrations of arsenic and lead, providing resourceful information that were compared and correlated to the data obtained by ICP-OES analysis. Sample preparation using microwave digestion technique was applied for the analyses by both techniques. Although the applied ICP-OES in-house method is suitable for determination of Hg, Cd, Co, V, and Ni, more sensitive technique such as ICP-MS is required for accurate determination of As and Pb concerning pharmaceuticals with high daily intakes.