Simultaneous quantitation of two direct acting hepatitis C antivirals (sofosbuvir and daclatasvir) by an HPLC-UV method designated for their pharmacokinetic study in rabbits


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Abstract

Sofosbuvir (SOF) and daclatasvir (DCS) are novel, recently developed direct acting antiviral agents characterized by potent anti-hepatitis C virus action. A fast and efficient HPLC-UV method was developed, validated and applied for simultaneous determination of SOF and DCS in pharmaceutical formulations and biological fluids based on coupling liquid-liquid extraction with ultrasound and dual wavelength detection at λmax; 260 and 313nm for SOF and DCS, respectively. This approach provided simple, sensitive, specific and cost-effective determination of the SOF-DCS mixture with good recoveries of the analytes from plasma. Analytes were separated within 7min on C18 analytical column with acetonitrile–10mM acetate buffer of pH 5.0 at a flow rate of 1.0mLmin−1. The linear ranges were 1–20μgmL−1 for SOF and 0.6–6μgmL−1 for DCS with correlation coefficients ≥0.9995. The detection limits in spiked rabbit plasma were 0.20 and 0.19μgmL−1 for SOF and DCS, respectively. The method was validated according to ICH and US-FDA guidelines. Finally, the method was successfully applied for simultaneous pharmacokinetic studies of SOF and DCS in rabbits using rofecoxib as internal standard.HIGHLIGHTSFast, simple and cost-effective HPLC–UV method was developed and validated for analysis of two novel hepatitis C antivirals.The proposed method was applied for pharmaceutical formulations and rabbit plasma analysis of sofosbuvir and daclatasvir.Liquid-liquid extraction coupled with ultrasound provided a simple and efficient extraction technique with better recovery.Dual wavelength detection greatly enhanced the sensitivity and specificity of method.The developed method was applied to simultaneous pharmacokinetic studies of sofosbuvir and daclatasvir in rabbit plasma.

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