Title

Green analytical method for the determination of sofosbuvir, ledipasvir, ribavirin and complex silymarin flavonoids simultaneously in biological fluids

Document Type

Article

Abstract

Hepatitis C virus (HCV) is the leading cause of liver cirrhosis and cancer worldwide. A recently developed anti-HCV regimen composed of sofosbuvir (SB), ledipasvir (LP), and ribavirin (RB) proved safe and effective against several viral phenotypes. On the other hand, silymarin (SY), a natural product with known histological and antiviral benefit in HCV patients, is commonly used as complementary medicine in this setting. Yet no studies exist to evaluate the possible interaction between these agents. Here, a green, rapid, sensitive LC–MS method was developed to simultaneously determine LP, SB, RB, and SY in biological samples. Separation was done on a Shimpack® XR – ODS II column with a gradient eluting solvent of methanol and 1% formic acid in water at a flow rate of 0.4 mL/min. Retention times were 2.0, 19.5, and 21.5 min for RB, SB and LP, respectively, while various SY peaks were resolved at 13.5, 14.3, 16.7, 17.13, 17.5, 18.2 and 18.5 min. The selected m/z values were 289, 481, 528 and 888 for RB, SY, SB and LP, respectively. The method was validated over concentration ranges of 10–2000 ng/mL, 10–2000, and 25–2000 ng/mL for RB, SB, and LP, respectively. The intra- and inter-day precision and accuracy of the quality control samples exhibited relative standard deviations < 15% with good accuracy. The method was applied to serum and liver homogenates obtained from rat groups receiving the anti-HCV regimen with or without SY. SY did not appear to affect absorption but significantly reduced liver uptake of the three drugs.

Publication Date

5-1-2021

Faculty

Faculty of Dentistry

Subject Area

Physical Sciences, General Chemistry

Indexed in Scopus

yes

Indexed in Web Of Science

yes

DOI

https://doi.org/10.1016/j.microc.2021.105964

Volume

164

Keywords

Hepatitis C virus, LC-MS, Ledipasvir, Ribavirin, Silymarin, Sofosbuvir

ISSN

0026265X

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