Was derived from Cf1368, which in turn was the fluorescent impurity Is the discovery of the antiviral (anti-Varicella zoster) lead, FVġ00: the development precursor of this water-soluble prodrug, Cf1743, Structure of this ethanesulfonoperoxoic acid derivative was revisedĪfter validation of the initial hit by NMR and LC–MS exhibitedĪ mismatch with the published structure, and HPLC was used to purify Is the selective nuclear factor κB inhibitor, NSC 676914: the The initial lead compound, an aminodihydroquinolone, turned out toīe the active ligand and high-potency (nM) inhibitor of kynurenineĪminotransferases, KAT II. Treatments of schizophrenia, where the N-hydroxylated impurity of Is from a drug discovery program driven by high-throughput screening, aimed at finding new Impurities in drug discovery and safety profiling. Of nature, similar considerations apply regarding the relevance of Typically more predictable than the combinatorial biosynthetic pathways While synthetic pathways in medicinal chemistry are The third case actually was discovered by The presence of ∼0.1% of epibatidine in the epiquinamide sample), 4 this demand most likely would not have been beyond

Would have required rather sensitive analysis (e.g., the authors estimated Than analytical approaches to uncover the problem, and while they 5 The first two instances used synthetic rather Lack of in vitro anti-TB potency in high-purity ursolic acid. Of the lead compound sesbanamide “hidden” in sesbanin, 2, 3 the more recent findings of inactive leads such as epiquinamideĬontaining the β 2-selective nicotinic acetylcholine Is perhaps most critical in the case of novel compounds to which aīiological activity is ascribed, because trace impurities of high Materials with assumed single chemical character. Organic substances of synthetic or natural origin, which can rangeįrom highly characterized reference materials to early stage experimental These considerations particularly apply to To apply identical or at least congruent standards to both experimentalĪnd clinical materials. For the purpose of producing new insight, it is important Of whether the material is designated as a research or pharmaceutical Of the chemical characterization to which it is assigned, regardless Consequently, the reproducibilityĪnd interpretability of research data always hinge on the accuracy Purity assessment is the logical prerequisite for the accurate characterization Of the true chemical constitution of a substance, Underlying concepts, provides a framework for standard qHNMR purityĪssays, and shows how adequate accuracy and precision are achieved Qualitative and (absolute) quantitative capability. To become practical 1H qNMR (qHNMR) procedures with simultaneous Widely accepted structural NMR workflows require minimal or no adjustments Absolute qNMR with flexible calibrationĬaptures analytes that frequently escape detection (water, sorbents). Uses nearly universal detection and provides a versatile and orthogonal With chromatography and elemental analysis, quantitative NMR (qNMR) Is particularly critical in discovery programs and wheneverĬhemistry is linked with biological and/or therapeutic outcome. Molecules, regardless of development stage (early discovery to approvedĭrug) and source (natural product or synthetic). A truthful description of chemical constitution requires coverage

Inmr student proof