Applications of grazing-angle reflection absorption Fourier transform infrared spectroscopy to the analysis of surface contamination.

Cleaning validation of pharmaceutical manufacturing equipment is required by legislation. Generally, wet chemical techniques are employed using swabbing and/or rinse sampling methods. These are generally either selective and time consuming, or less selective and give results in a shorter period. The infrared reflection absorption spectroscopy (IRRAS) technique explored here attempts to deliver accurate, selective surface contamination information in real time to complement current methods and reduce down-time. The IRRAS instrument used in this research is a Fourier transform infrared (FTIR) spectrometer coupled by an IR fibre-optic cable to a grazing-angle sampling head with a fixed incidence angle of 80°. The introduced flexibility permits collection of in situ spectra from contaminated surfaces. Calibration models are developed using the multivariate, linear partial least squares (PLS) statistical method. The research focuses on sodium dodecyl sulfate (SDS), a model cleaning agent, on metal (aluminium and stainless steel) and dielectric (glass, EPDM and silicone) surfaces. The effects of surface finish are investigated for SDS on stainless steel. Calibrations for SDS and paracetamol in the presence of each other on glass surfaces are examined, as well as a common industrial cleaner (P3 cosa PUR80) on polished stainless steel. For the calibration sets in this thesis, RMSECV values were < 0.41 μg cm, corresponding to conservative surface residues detection limits of better than ~0.86 μg cm. However, RMSECV values depend on the calibration loading range, and the detection limits were typically ~0.2 μg cm for loading ranges 0–2.5 μg cm. These are below visual detection limits, generally taken to be 1–4 μg cm, depending on the analyte and substrate. This shows that IRRAS is a viable method for the real-time detection and quantification of surface contamination by surfactants and active pharmaceutical ingredients on metals and dielectrics. Acknowledgements First and foremost I would like to thank my Ph.D. supervisors: Peter Harland and Bryce Williamson, since without your encouragement, guidance and friendship the completion of this thesis would not have been possible. I would also like to thank the present and past members of the Harland-Williamson group: Ben, Josh and James, for your friendship and stimulating discussions during the course of my research. I have greatly enjoyed my time at the University of Canterbury this is in no small part due to the people I have met here; your friendships have been very much appreciated. The Department of Chemistry is fortunate to have many talented technical staff, from whom I have been able to learn during my research. Much of the construction and repairs completed during this were carried out by the mechanical workshop boys; special thanks goes to Danny Leonard. The NMR section of my research would also not have been possible if it was not for the guidance of Martin Lee. Thanks also go to Mary Thomson and Peter Melling for their support, especially in the initial stages of the project. Acknowledgement also goes to their company, Remspec Corporation, Massachusetts, for the provision of a graduate student scholarship and for the provision of equipment and software, without which this project would not have started. I would also like to thank the University of Canterbury Evans’ Fund, the New Zealand Institute of Chemistry (NZIC) and the New Zealand Federation of Graduate Women (NZEGW) for the provision of funds which have allowed me to travel to a number of conferences both in New Zealand and overseas. A final big thank you goes to my family and James, the task of completing this thesis would not have been possible if it was not for the love, support and patience you have shown me over the years. List of publications 1. Grazing-Angle Fiber-Optic Fourier-Transform Infrared Reflection-Absorption Spectroscopy for the in situ Detection and Quantification of Two Active Pharmaceutical Ingredients on Glass. Perston, Benjamin B. ; Hamilton, Michelle L. ; Harland, Peter W. ; Williamson, Bryce E. , Thomson, Mary A. ; Melling, Peter J. Analytical Chemistry, 2007, 79(3), 1231-1236. 2. Fiber-Optic Infrared Reflection-Absorption Spectroscopy for Trace Analysis on Surfaces of Varying Roughness: Sodium Dodecyl Sulfate on Stainless Steel. Hamilton, Michelle L. ; Perston, Benjamin B. ; Harland, Peter W. ; Williamson, Bryce E. , Thomson, Mary A. ; Melling, Peter J. Applied Spectroscopy, 2006, 60(5), 516-520. 3. Grazing-Angle Fiber-Optic Infrared Reflection-Absorption Spectroscopy for in Situ Cleaning Validation. Hamilton, Michelle L. ; Perston, Benjamin B. ; Harland, Peter W. ; Williamson, Bryce E. , Thomson, Mary A. ; Melling, Peter J. Organic Process Research & Development, 2005, 9(3), 337-343. 4. Synthesis, structures and rac/meso isomerization behaviour of bisplanar chiral bis(phosphino-η5-indenyl)iron(II) complexes. Curnow, Owen J.; Fern, Glen M. ; Hamilton, Michelle L. ; Jenkins, Elizabeth M. Journal of Organometallic Chemistry, 2004, 689(11), 1897-1910. 5. Mechanistic Studies on a Facile Ring-Flipping Process in Planar Chiral Ferrocenes under Ambient and High Pressure and Its Relevance to Asymmetric Catalysis. Curnow, Owen J.; Fern, Glen M. ; Hamilton, Michelle L. ; Zahl, Achim; van Eldik, Rudi. Organometallics, 2004, 23(4), 906-912. LIST OF PUBLICATIONS 6. Absolute electron impact ionization cross-sections for the C1 to C4 alcohols. Hudson, James E. ; Hamilton, Michelle L. ; Vallance, Claire; Harland, Peter W. Physical Chemistry Chemical Physics, 2003, 5(15), 3162-3168. 7. Oxide, Sulfide, Selenide, and Borane Derivatives of Indenylphosphines. Adams, Julian J.; Berry, David E. ; Curnow, Owen J.; Fern, Glen M. ; Hamilton, Michelle L. ; Kitto, Heather J.; Pipal, J. Robert. Australian Journal of Chemistry, 2003, 56(11), 11531160.