Validated 1H and 19F nuclear magnetic resonance for the quantitative determination of the hepatitis C antiviral drugs sofosbuvir, ledipasvir, and daclatasvir in tablet dosage forms

Abstract

Use of quantitative NMR (qNMR) is increasing nowadays for the determination of active pharmaceutical drugs in their bulk drug raw materials and in pharmaceutical formulations. In the present study, the advantages of two techniques of qNMR were exploited to assay three anti-hepatitis drugs, namely, daclatasvir by 1H-NMR, sofosbuvir, and ledipasvir by 19F-NMR in bulk drugs and in tablet dosage forms. The method was performed using phloroglucinol and norfloxacin as internal standards for 1H-NMR and 19F-NMR, respectively. Dimethyl sulfoxide-d6 (DMSO-d6) was utilized as the qNMR solvent throughout the study. The obtained quantitative signals were adjusted comparative to the DMSO-d6 signal at 2.49 ppm. The selected singlet quantitative signal of DAC was at 8.13 ppm whereas the singlet quantitative signals of phloroglucinol anhydrous were at 5.64 ppm and 8.94 ppm. Whereas, the selected singlet quantitative fluorine signals of SOF and LED were at -158.67 ppm and −108.38 ppm, correspondingly, while the quantitative fluorine signal of norfloxacin was selected at -121.27 (singlet). The methods were validated in accordance with the guidelines of the International Conference on Harmonization (ICH). The linearity range was in the range of 2–24 mg/mL for all drugs. The LOD was found to be 0.309, 0.387, 0.275 mg/mL and the LOQ was found to be 1.029, 1.289 and 0.915 mg/mL for daclatasvir, sofosbuvir, and ledipasvir, correspondingly. Robustness was investigated through varying diverse factors. The results obtained were found nearly similar when compared to a reference HPLC method. The developed technique was found to be easy, rapid and precise with respect to other analytical techniques.