Purity determination of a new antifungal drug candidate using quantitative 1H NMR spectroscopy : method validation and comparison of calibration approaches.

Abstract

Quantitative nuclear magnetic resonance (qNMR) is an analytical technique that offers numerous advantages in pharmaceutical applications including minimum sample preparation and rapid data collection times with no need for response factor corrections, being a powerful tool for assaying drug content in both drug discovery and early drug development. In the present work, we

have applied qNMR, using both the internal standard and the electronic refer- ence to access in vivo concentrations 2 calibration methods, to assess the purity

of RI76, a novel antifungal drug candidate. NMR acquisition and processing parameters were optimized in order to obtain spectra with intense, well‐

resolved signals of completely relaxed nuclei. The analytical method was vali- dated following current guidelines, demonstrating selectivity, linearity, accu- racy, precision, and robustness. The calibration approaches were statistically

compared, and no significant difference was observed when comparing the obtained results and their dispersion in terms of relative standard deviation. The proposed qNMR method may, therefore, be used for both qualitative and

quantitative assessments of RI76 in early drug development and for character- ization of this compound.