Quantum mechanical NMR full spin analysis in pharmaceutical identity testing and quality control

• Published in: Journal of pharmaceutical and biomedical analysis 2021-01, Vol.192, p.113601-113601, Article 113601
• Main Authors: Achanta, Prabhakar S., Jaki, Birgit U., McAlpine, James B., Friesen, J. Brent, Niemitz, Matthias, Chen, Shao-Nong, Pauli, Guido F.
• Format: Article
• Language: English
• Subjects: 1H NMR spectroscopy (HNMR); Calculated NMR spectra; Hydrogen; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Pharmaceutical Preparations; Quality Control; Quantum mechanics; Signal multiplicity; Simulated NMR spectra
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2020.113601

•NMR evaluates APIs and their impurities on a nuclear basis.•1H NMR is rich in quantitative and qualitative information technique.•1H Full Spin Analysis leverages all information using quantum mechanics (QM).•QM-based analysis dereplicates and precisely quantifies complex NMR signals. Issues related to pharmaceutical quality are arising at an alarming rate. Pharmaceutical quality concerns both the Active Pharmaceutical Ingredients (APIs) and the Finished Drug Product/ Formulation. Recently, there has been a significant increase in the number of reports of harmful impurities in marketed drug formulations. Impurities range from solvents, reactants, adulterants, and catalysts to synthetic byproducts. Quality concerns in commercial preparations may also arise due to shelf life stability. Furthermore, a number of falsified and substandard drug cases have been reported. Most of the techniques which are currently in place can, at best, detect the impurities, but cannot identify them unless they are already known and can be compared to a standard. On the other hand, 1H NMR spectroscopy detects all the hydrogen containing species, typically provides information to elucidate structures partially or even completely, and through its absolute quantitative capabilities even can detect the presence hydrogen-free species indirectly. The structural properties that produce 1H NMR signals as characteristic representations of a given molecule are the chemical shifts (δ in ppm) and coupling constants (J in Hz). Along with the line widths (ω1/2 in Hz), these parameters are bound to both the molecule and the NMR experimental conditions by quantum mechanical (QM) principles. This means that the 1H NMR spectra of APIs can be precisely calculated and compared to the experimental data. This review explains how 1H NMR spectroscopy coupled with Full Spin Analysis can contribute towards the quality control of pharmaceuticals by improving structural dereplication and achieving simultaneous quantification of both APIs and their contaminants.