title: Survey and qualification of internal standards for quantification by 1H NMR spectroscopy.
abstract: In quantitative NMR (qNMR) selection of an appropriate internal standard proves to be crucial. In this study, 25 candidate compounds considered to be potent internal standards were investigated with respect to the ability of providing unique signal chemical shifts, purity, solubility, and ease of use. The (1)H chemical shift (delta) values, assignments, multiplicities and number of protons (for each signal), appropriateness (as to be used as internal standards) in four different deuterated solvents (D(2)O, DMSO-d(6), CD(3)OD, CDCl(3)) were studied. Taking into account the properties of these 25 internal standards, the most versatile eight compounds (2,4,6-triiodophenol, 1,3,5-trichloro-2-nitrobenzene, 3,4,5-trichloropyridine, dimethyl terephthalate, 1,4-dinitrobenzene, 2,3,5-triiodobenzoic acid, maleic acid and fumaric acid) were qualified using both differential scanning calorimetry (DSC) and NMR spectroscopy employing highly pure acetanilide as the reference standard. The data from these two methods were compared as well as utilized in the quality assessment of the compounds as internal standards. Finally, the selected internal standards were tested and evaluated in a real case of quantitative NMR analysis of a paracetamol pharmaceutical product.
authors.affiliation: Medical Products Agency, P.O. Box 26, SE-75103 Uppsala, Sweden. torgny.rundlof@mpa.se
authors.forename: Torgny
authors.initials: T
authors.lastname: Rundlöf
authors.forename: Marie
authors.initials: M
authors.lastname: Mathiasson
authors.forename: Somer
authors.initials: S
authors.lastname: Bekiroglu
authors.forename: Birgit
authors.initials: B
authors.lastname: Hakkarainen
authors.forename: Tim
authors.initials: T
authors.lastname: Bowden
authors.forename: Torbjörn
authors.initials: T
authors.lastname: Arvidsson
mesh_terms: D000083:Acetanilides / Q000032:analysis; D002152:Calorimetry, Differential Scanning; D009682:Magnetic Resonance Spectroscopy / Q000592:standards*; D012015:Reference Standards
chemical_list: D000083:Acetanilides; C508827:acetanilide