title: Determination of the purity of pharmaceutical reference materials by 1H NMR using the standardless PULCON methodology.
abstract: A fast and reliable nuclear magnetic resonance spectroscopic method for quantitative determination (qNMR) of targeted molecules in reference materials has been established using the ERETIC2 methodology (electronic reference to access in vivo concentrations) based on the PULCON principle (pulse length based concentration determination). The developed approach was validated for the analysis of pharmaceutical samples in the context of official medicines control, including ibandronic acid, amantadine, ambroxol and lercanidipine. The PULCON recoveries were above 94.3% and coefficients of variation (CVs) obtained by quantification of different targeted resonances ranged between 0.7% and 2.8%, demonstrating that the qNMR method is a precise tool for rapid quantification (approximately 15min) of reference materials and medicinal products. Generally, the values were within specification (certified values) provided by the manufactures. The results were in agreement with NMR quantification using an internal standard and validated reference HPLC analysis. The PULCON method was found to be a practical alternative with competitive precision and accuracy to the classical internal reference method and it proved to be applicable to different solvent conditions. The method can be recommended for routine use in medicines control laboratories, especially when the availability and costs of reference compounds are problematic.
authors.affiliation: Chemisches und Veterinäruntersuchungsamt (CVUA) Karlsruhe, Weissenburger Strasse 3, 76187 Karlsruhe, Germany; Bruker Biospin GmbH, Silberstreifen, 76287 Rheinstetten, Germany; Institute of Chemistry, Saratov State University, Astrakhanskaya Street 83, 410012 Saratov, Russia.
authors.forename: Yulia B
authors.initials: YB
authors.lastname: Monakhova
authors.affiliation: Chemisches und Veterinäruntersuchungsamt (CVUA) Karlsruhe, Weissenburger Strasse 3, 76187 Karlsruhe, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Kohl-Himmelseher
authors.affiliation: Chemisches und Veterinäruntersuchungsamt (CVUA) Karlsruhe, Weissenburger Strasse 3, 76187 Karlsruhe, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kuballa
authors.affiliation: Chemisches und Veterinäruntersuchungsamt (CVUA) Karlsruhe, Weissenburger Strasse 3, 76187 Karlsruhe, Germany. Electronic address: Lachenmeier@web.de.
authors.forename: Dirk W
authors.initials: DW
authors.lastname: Lachenmeier
mesh_terms: D000547:Amantadine / Q000032:analysis; D000551:Ambroxol / Q000032:analysis; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D004095:Dihydropyridines / Q000032:analysis; D004164:Diphosphonates / Q000032:analysis; D004340:Drug Contamination; D000077557:Ibandronic Acid; D008956:Models, Chemical; D004364:Pharmaceutical Preparations / Q000032:analysis* / Q000592:standards; D066244:Proton Magnetic Resonance Spectroscopy / Q000592:standards*; D012015:Reference Standards; D015203:Reproducibility of Results; D013678:Technology, Pharmaceutical / Q000379:methods / Q000592:standards*
chemical_list: D004095:Dihydropyridines; D004164:Diphosphonates; D004364:Pharmaceutical Preparations; D000551:Ambroxol; D000547:Amantadine; D000077557:Ibandronic Acid; C060343:lercanidipine
keywords: (1)H NMR; Amantadine; Amantadine (PubChem CID: 2130); Ambroxol; Ambroxol (PubChem CID: 2132); Ibandronic acid; Ibandronic acid (PubChem CID: 60852); Lercanidipine (PubChem CID: 65866); PULCON methodology