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

✍ Scribed by Martin Sandvoss; Ben Bardsley; Tony L. Beck; Emma Lee-Smith; Stephanie E. North; Peter J. Moore; Andrew J. Edwards; Richard J. Smith

• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: English
• Weight: 307 KB
• Volume: 43
• Category: Article
• ISSN: 0749-1581
• DOI: 10.1002/mrc.1615

✦ Synopsis

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. Copyright © 2005 John Wiley & Sons, Ltd.