Spectrophotometric Methods for Simultaneous Determination of Sofosbuvir and Ledipasvir (HARVONI Tablet): Comparative Study with Two Generic Products

Abstract

Abstract Sofosbuvir and ledipasvir are the first drugs in a combination pill to treat chronic hepatitis C virus. Simple, sensitive, and rapid spectrophotometric methods are presented for the determination of sofosbuvir and ledipasvir in their combined dosage form. These methods were based on direct measurement of ledipasvir at 333 nm (due to the lack of interference of sofosbuvir) over a concentration range of 4.0–14.0 µg/mL, with a mean recovery of 100.78 ± 0.64%. Sofosbuvir was determined, without prior separation, by third-derivative values at 281 nm; derivative ratio values at 265.8 nm utilizing 5.0 µg/mL ledipasvir as a divisor; the ratio difference method using values at 270 and 250 nm using 5.0 µg/mL ledipasvir as a divisor; and the ratio subtraction method using values at 261 nm. These methods were found to be linear for sofosbuvir over a concentration range of 5.0–35.0 µg/mL. The suggested methods were validated according to International Conference on Harmonization guidelines. Statistical analysis of the results showed no significant difference between the proposed methods and the manufacturer's LC method of determination with respect to accuracy and precision. These methods were used to compare the equivalence of an innovator drug dosage form and two generic drug dosage forms of the same strength.