Category: Formulation and Quality
Purpose: As part of the oversight to maintain the safety of pharmaceuticals, there are extensive efforts to test for extractables and leachables in drug packaging. The goal is to identify their composition in order to insure that patients are not exposed to toxic products. Testing involves exposure of the container to conditions designed to accelerate the release of foreign material, ie., elevated temperature and solvent extraction.
Methods: When the identification of heavy metals is the goal analysis by elemental techniques such as ICP (inductively coupled plasma emission spectroscopy), XRF (X-ray fluorescence) and XPS (X-ray photoelectron spectroscopy) has been employed. For identification of organic materials, MS (mass spectroscopy) and IR (infrared spectroscopy) have been employed. Note that ICP and MS are both destructive methods. The sample is gone after the measurement. XPS requires preparation for an electron microscope. IR is a good tool for studying organic materials, but for trace analysis there may be limitations due to the dimensions of the collected material; that is spatial resolution for IR microscopy is not better than about 20-30mm. In addition, standard benchtop instruments cut-off at about 650 cm-1 which limits the information available on many inorganic phases.
Results: Raman analysis of extractables and leachables - Raman microscopy provides analytical advantages with capabilities not available in the above cited techniques. Sample preparation is minimal, spatial resolution is better than 1mm, and standard instruments can provide molecular and crystalline information on both organic and almost all inorganic materials.
Three samples of extracted solid material in saline were supplied in saline by American Preclinical Services. They presented as three different colors – green, pink and orange. Using the XGT 7000 we performed XRF elemental analysis and found the elements listed below.