title: Importance of purity evaluation and the potential of quantitative ¹H NMR as a purity assay.
abstract: In any biomedical and chemical context, a truthful description of chemical constitution requires coverage of both structure and purity. This qualification affects all drug molecules, regardless of development stage (early discovery to approved drug) and source (natural product or synthetic). Purity assessment is particularly critical in discovery programs and whenever chemistry is linked with biological and/or therapeutic outcome. Compared with chromatography and elemental analysis, quantitative NMR (qNMR) uses nearly universal detection and provides a versatile and orthogonal means of purity evaluation. Absolute qNMR with flexible calibration captures analytes that frequently escape detection (water, sorbents). Widely accepted structural NMR workflows require minimal or no adjustments to become practical ¹H qNMR (qHNMR) procedures with simultaneous qualitative and (absolute) quantitative capability. This study reviews underlying concepts, provides a framework for standard qHNMR purity assays, and shows how adequate accuracy and precision are achieved for the intended use of the material.
authors.affiliation: Department of Medicinal Chemistry and Pharmacognosy and ‡Institute for Tuberculosis Research, College of Pharmacy, University of Illinois at Chicago , 833 S. Wood Street, Chicago, Illinois 60612, United States.
authors.forename: Guido F
authors.initials: GF
authors.lastname: Pauli
authors.forename: Shao-Nong
authors.initials: SN
authors.lastname: Chen
authors.forename: Charlotte
authors.initials: C
authors.lastname: Simmler
authors.forename: David C
authors.initials: DC
authors.lastname: Lankin
authors.forename: Tanja
authors.initials: T
authors.lastname: Gödecke
authors.forename: Birgit U
authors.initials: BU
authors.lastname: Jaki
authors.forename: J Brent
authors.initials: JB
authors.lastname: Friesen
authors.forename: James B
authors.initials: JB
authors.lastname: McAlpine
authors.forename: José G
authors.initials: JG
authors.lastname: Napolitano
mesh_terms: D002138:Calibration; D002626:Chemistry, Pharmaceutical / Q000379:methods* / Q000592:standards; D002845:Chromatography / Q000379:methods; D004340:Drug Contamination; D009682:Magnetic Resonance Spectroscopy / Q000379:methods* / Q000592:standards; D012015:Reference Standards; D015203:Reproducibility of Results; D013678:Technology, Pharmaceutical / Q000592:standards