Research on the synthesis of generic drug - letrozole on a scale of 100 g per batch conforming to the United State Pharmacopeia (USP38)

Abstract

In this research, letrozole, on a scale of 100 g/batch, was successfully synthesized via the reaction between 4-[1-(1,2,4-triazolyl)methyl] benzonitrile (TMB) and p-fluorobenzonitrile, with the aid of deprotonated agent called potassium tert-butoxide (t-BuOK) dissolved in tetrahydrofuran (THF). The crude letrozole was recrystallized twice using the mixture of n-hexane:ethyl acetate (the ratio 3:1). The chemical structure and properties of the obtained product were characterized by nuclear magnetic resonance spectroscopy (1H-NMR and 13C-NMR) and mass spectroscopy (MS). Standards of detection (Fourier transform infrared (FTIR), high performance liquid chromatography (HPLC)) and quantification (HPLC), impurities, and the standard amount of water conformed in the United State Pharmacopeia (USP 38) were also examined. According to the results, the purity of letrozole was 99.79%; besides, other criterions also met the quality standard of USP 38. Both stability test and accelerated aging test showed that the synthesized letrozole had the shelf life of more than 2 years.