Impurities, trace level structural identification

Traditional methodologies for structural identification of trace level impurities in drng substances/products usually involve fractionation of each impurities using a scaled-np analytical chromatographic method, followed by off-line spectroscopic analysis. Coupling of HPLC separation and electrospray mass spectrometry allows on-line acquisition of full scan mass spectra and generation of tandem mass spectrometric data. LC/ESI MS has revolntionized trace analysis for qnalitative and quantitative studies in pharmaceutical analysis. 

Chen, G., Khusid, A., Daaro, I., Irish, P., and Pramanik, B. N. (2007). Structural identification of trace level enol tautomer impurity by on-line hydrogen/deuterium exchange HR-LC/MS in a LTQ-Orbitrap hybrid mass spectrometer. J. Mass Spectrom. 42 967-970. 

The ability of modern analytical chemistry to identify and quantify impurities in pharmaceutical products is staggering. It is now routine to elucidate organic impurity structures below the 0.1 %o level, which has led to an increased ability to detect and identify those chemical entities of potential concern for the safety and efficacy of pharmaceuticals. New developments, such as hybrid MS systems and LC/NMR when fully integrated into the MS-based paradigm, hold the promise of increased efficiency for trace impurity identification with resulting efficiency increases in the overall pharmaceutical development process. 

For Fe oxides, FTIR spectroscopy provides a rapid means of identification. It can detect traces (1-2%) of goethite in a sample of hematite. In addition, low levels of impurities arising from insufficient washing, for example nitrate in ferrihydrite (band at 1384 cm ) and carbonate in goethite (ca. 1300 and 1500 cm ) can be detected. Broadening of the absorption bands reflects a decrease in crystal perfection (Cambier, 1986). Structural substitution of Fe by A1 (Schulze Schwertmann, 1984), Mn (Stiers Schwertmann 1985), and Cr (Schwertmann et al. 1989) causes a shift in the positions of the bands. 

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