Plain 1 H NMR Analysis Streamlines the Quality Control of Antiviral Favipiravir and Congeneric WHO Essential Medicines.

Achanta, Prabhakar S; Chen, Shao-Nong; Pauli, Guido F

Favipiravir is an established antiviral currently assessed as an investigational drug for the treatment of COVID-19. Favipiravir is strikingly similar to two molecules that WHO lists as essential medicines, which also consist of a six-membered aromatic N-heterocycle bearing a carboxamide function: the anti-tuberculosis agent, pyrazinamide, and nicotinamide, aka vitamin B3 . We demonstrate the utility of 1 H NMR profiling, an emerging pharmacopoeial tool, for the highly specific identification, selective differentiation of congeners, and subsequent detection of drug falsification or adulteration of these medicines. The straightforward comparison of basic 1D 1 H NMR spectra, obtained with benchtop or advanced NMR instruments alike, offers a rapid identity assay and works independently of physical reference materials. This approach accelerates and advances pharmaceutical quality control measures under situations of increased drug demand and altered economy, such as during a pandemic.