Confocal Raman Microscopy in Forensic Pharmaceutical Investigations

Scanning electron microscopy with energy dispersive X-ray spectrometry (SEM-EDS) and Fourier-transform infrared microspectrophotometry (micro-FT-IR) have been widely demonstrated as complementary analytical tools for the identification of complex mixtures and unknown materials. However, there is a gap between the information provided by these two techniques. Even though elemental and morphological information is obtained on small single particles with SEM-EDS technology, no molecular or structural information is available. Likewise, although chemical information can be acquired using FT-IR, analysis of small single particles is significantly limited. We applied confocal Raman microscopy (CRM) in our laboratory to bridge the gap between FT-IR and SEM, and it provided chemical and vibrational information on a scale approaching the resolution of an SEM. In one application, monomer solutions used during a contact lens manufacturing process exhibited haze that was related to particulate contamination. The particles were isolated and analyzed by CRM, SEM, and micro-FT-IR. The particle size range was about 1-500 mu m. Particles <50 mu m were analyzed and identified by Raman spectroscopy and SEM. Particles >50 mu m were analyzed and identified by micro-FT-IR and SEM. Numerous materials associated with the manufacturing process of the monomer were identified, as well as foreign materials. The identification of the particulate materials causing the haze of the monomer assisted the manufacturer in determining the sources of the contamination and improving the quality of the product.