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HPLC-SPE-NMR in pharmaceutical development: capabilities and applications
Journal article   Peer reviewed

HPLC-SPE-NMR in pharmaceutical development: capabilities and applications

Martin Sandvoss, Ben Bardsley, Tony L Beck, Emma Lee-Smith, Stephanie E North, Peter J Moore, Andrew J Edwards and Richard J Smith
Magnetic resonance in chemistry, Vol.43(9), pp.762-770
09/2005
DOI: 10.1002/mrc.1615
PMID: 16049946

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Abstract

High-performance liquid chromatography-solid phase extraction-NMR spectroscopy (HPLC-SPE-NMR) has recently become commercially available and has been evaluated with regard to its applicability in a pharmaceutical environment. The addition of an automated SPE unit to an HPLC-NMR system for peak trapping results in an improved NMR signal-to-noise ratio (S/N) and also has other practical advantages. The trapping efficiency is shown to depend on compound polarity and is highest for compounds eluting late on reversed-phase HPLC systems. Multiple peak trapping further increases the S/N, again with the best results for less polar compounds. For polar compounds, multiple peak trapping resulted in no S/N gain as the amount of material retained on the SPE cartridge was equivalent to that from a single injection. When compared with conventional HPLC-NMR, a S/N gain of up to five-fold could be achieved for some compounds in a single trapping step. A major advantage of the technique is the independence of the chromatographic step from the NMR step, resulting in greater versatility than conventional HPLC-NMR in the HPLC solvents and NMR solvents that can be used. Practical applications from both drug metabolite and drug impurity identification are presented.
Chromatography, High Pressure Liquid - methods Magnetic Resonance Spectroscopy - methods Solvents - chemistry Acids, Carbocyclic - chemistry Bile - chemistry Rats Bile - metabolism Ketones - analysis Animals Acids, Carbocyclic - analysis Sensitivity and Specificity Dogs Ketones - chemistry Pharmaceutical Preparations - chemistry Acetonitriles - chemistry Pharmaceutical Preparations - analysis

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