title: HPLC-SPE-NMR in pharmaceutical development: capabilities and applications.
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.
authors.affiliation: DMPK Structural ID Group, GlaxoSmithKline R & D, Ware, UK. martin.x.sandvoss@gsk.com
authors.forename: Martin
authors.initials: M
authors.lastname: Sandvoss
authors.forename: Ben
authors.initials: B
authors.lastname: Bardsley
authors.forename: Tony L
authors.initials: TL
authors.lastname: Beck
authors.forename: Emma
authors.initials: E
authors.lastname: Lee-Smith
authors.forename: Stephanie E
authors.initials: SE
authors.lastname: North
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Moore
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Edwards
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Smith
mesh_terms: D000097:Acetonitriles / Q000737:chemistry; D000146:Acids, Carbocyclic / Q000032:analysis / Q000737:chemistry; D000818:Animals; D001646:Bile / Q000737:chemistry / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004285:Dogs; D007659:Ketones / Q000032:analysis / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D004364:Pharmaceutical Preparations / Q000032:analysis* / Q000737:chemistry; D051381:Rats; D012680:Sensitivity and Specificity; D012997:Solvents / Q000737:chemistry
chemical_list: D000097:Acetonitriles; D000146:Acids, Carbocyclic; D007659:Ketones; D004364:Pharmaceutical Preparations; D012997:Solvents; C032159:acetonitrile