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

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.

Validated Reversed-Phase Liquid Chromatographic Method with Gradient Elution for Simultaneous Determination of the Antiviral Agents: Sofosbuvir, Ledipasvir, Daclatasvir, and Simeprevir in Their Dosage Forms

“…Statistical comparisons between the results of the proposed method on pharmaceutical dosage forms and those of reported methods [ 27 , 31 , 38 ] were carried out using Student’s t -test for accuracy and F -test for precision. As shown in Table 6 , the calculated t -test and F -values did not exceed the tabulated one at the 95% confidence level, revealing that there was no significant difference between the proposed and reported methods with respect to accuracy and precision.…”

“…Several methods for the simultaneous determination of SF either with LD [ 19 , 33 , 34 , 35 , 36 , 37 , 38 ] or with SM have been published [ 13 ]. A single method has been published for the simultaneous determination of SF, LD, DC, and SM in plasma [ 39 ].…”

In depth investigation of quantitative analytical and bioanalytical techniques of hepatitic drug sofosbuvir in different matrices: a review

“…The adopted methods were also validated as per ICH guidelines and statistically compared to an inhouse HPLC method. 25 Abo T et al 26 has developed spectrophotometric methods for simultaneous determination of Sofosbuvir and Ledipasvir . These methods were based on direct measurement of ledipasvir at 333nm.…”

“…The analytical method was validated for various parameters as per ICH guidelines. 26 Chromatographic methods: The high performance liquid chromatography (HPLC) method has been reported for the analysis of Sofosbuvir in pharmaceutical formulation, bulk as well as in biological fluids.…”

Pharmacokinetic evaluation of daclatasvir and ledipasvir in healthy volunteers using a validated highly sensitive spectrofluorimetric method

“…A literature review revealed a few methods have been reported for the quantitative determination of DAC and LED alone or in combination with other drugs. These include spectrophotometric, spectrofluorimetric, HPLC,, LC–MS/MS and electrochemical methods . The extensive use of the newly discovered antiviral drugs for the treatment of HCV necessitates the need to develop a cheap, rapid bio‐analytical method for their routine measurement in biological samples.…”