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

Abstract

A simple, highly sensitive and selective spectrofluorimetric method has been developed and fully validated for the determination of daclatasvir (DAC) and ledipasvir (LED) in tablets and human plasma. The method is based on measurement of the native fluorescence in methanol at λ 384 nm after excitation at λ 318 nm for DAC and in acetonitrile at λ 402 nm after excitation at λ 340 nm for LED. The fluorescence intensity (FI) concentration plot was rectilinear over the ranges 1.2-12, 0.1-18 ng ml and 9-90, 1-100 ng ml with a good correlation of r = 0.9994 to r = 0.9997 in standard solution and human plasma for DAC and LED, respectively. The extraction of analytes from plasma was performed using methanol and acetonitrile as a precipitating agent with lower limit of quantification (LLOQ) of 0.1 and 1.0 ng ml for DAC and LED; respectively. The proposed method was validated according to the US Food and Drug Administration (FDA) guidelines and successfully applied for estimating the pharmacokinetic parameters of DAC and LED following oral administrations of their tablets.

Micellar‐based spectrofluorimetric method for the selective determination of ledipasvir in the presence of sofosbuvir: application to dosage forms and human plasma

“…Recently (October 2014), a ledipasvir/sofosbuvir combination was approved by the US Food and Drug Administration as a fixed‐dose tablet taken once daily for the treatment of chronic HCV 1 with or without cirrhosis . Due to its recent introduction into the market, few techniques have been reported for the estimation of LDS including chromatographic, spectrophotometric, and spectrofluorimetric methods . Although the reported chromatographic techniques are sensitive enough, they are subject to extraction procedures as the plasma samples contain a high content of phospholipids as well as the techniques requiring expensive organic solvents and long operating times.…”