Electron paramagnetic resonance spectroscopy studies of oxidative degradation of an active pharmaceutical ingredient and quantitative analysis of the organic radical intermediates using partial least-squares regression.
Electron paramagnetic resonance (EPR) spectroscopy was used to study the radical species formed during the oxidation of an active pharmaceutical ingredient in the solid state. It was found that the extent of radical generation correlated to the formation of an oxidative degradation product. Multifrequency EPR and electron nuclear double resonance spectroscopy gave additional information on the identity of the organic radical species involved in the oxidation process, and a mechanism was proposed for the degradation, involving the formation of both carbon-centered and peroxy radicals. The multivariate analysis technique of partial least-squares (PLS) regression was then used to determine the extent of oxidation of the active pharmaceutical ingredient from the EPR spectra. The suitability of this approach was demonstrated from its application to a series of standards. The conventional approach for the quantitative analysis of EPR spectra is to measure the peak height or to perform double integration of the spectral region containing the signal of interest. Both of these methods have intrinsic errors associated with them, particularly for weak EPR signals with a poor signal-to-noise ratio or a sloping background response. The results obtained showed that greatly improved quantitation was obtained using the PLS regression approach.
Williams
Helen Elizabeth
HE
AstraZeneca, Silk Road Business Park, Macclesfield, Cheshire SK10 2NA, UK. Helen.Williams@AstraZeneca.com
Loades
Victoria Catherine
VC
Claybourn
Mike
M
Murphy
Damien Martin
DM
D000438:Alcohols / Q000737:chemistry; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods*; D005609:Free Radicals / Q000737:chemistry; D016018:Least-Squares Analysis; D010084:Oxidation-Reduction; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012044:Regression Analysis
D000438:Alcohols; D005609:Free Radicals; D004364:Pharmaceutical Preparations