Mark Nicholas, Associate Principal Scientist in Imaging, Pharmaceutical Development, AstraZeneca R&D Mölndal

Research interests: Imaging and surface analysis of pharmaceutical solids

My central research tool is TOF-SIMS (time-of-flight secondary ion mass spectrometry). It is a surface mass spectrometry technique. It has high lateral resolution (<1µm) and high depth resolution (<1nm). Other surface analysis and imaging techniques I use to characterize pharmaceutical solids include XPS (X-ray photoelectron spectroscopy), fluorescence microscopy including CLSM (confocal laser scanning microscopy), and AFM (atomic force microscopy). Samples analyzed include unformulated, partially formulated, and fully formulated active pharmaceutical ingredients (API).

We are increasing our use of multivariate image creation techniques to maximize contrast between chemical domains. Each pixel in a TOF-SIMS spectrum has a mass spectrum associated with it. Traditionally, one images the pixel-to-pixel intensity variations of an ion characteristic of a particular chemical domain. Alternatively, one can image a weighted sum of many or all of the peaks in the spectrum for each chemical domain. We currently use PCA (principal components analysis) followed by Varimax rotation of the PCA loadings to produce start vectors for MCR (multivariate curve resolution). An image created from the MCR values at each pixel generally gives us better contrast between chemical domains than does the imaging of one or a few characteristic ions.