A Quick and Sensitive LC-MS/MS Method for Simultaneous Quantification of Sofosbuvir Metabolite (GS-331007) in Human Plasma: Application to Hepatitis C Infected Patients with End-Stage Renal Disease

TL;DR

A new LC-MS/MS method was developed to measure sofosbuvir metabolite in plasma, showing its effectiveness in patients with hepatitis C and kidney disease.

Contribution

An optimized LC-MS/MS method for quantifying sofosbuvir metabolite in plasma with high sensitivity and speed.

Findings

The developed method detected SOF-007 with a limit of detection of 2.3 in plasma.

Plasma concentrations of SOF-007 decreased significantly after dialysis in patients with ESRD.

SOF-007 showed minimal cumulative effect in patients with ESRD compared to healthy controls.

Abstract

Sofosbuvir (SOF) is a revolutionary treatment for patients with hepatitis C virus (HCV). However, its efficacy and safety among patients with end-stage renal disease (ESRD) remains controversial. In this study, we examined the levels of SOF metabolite (GS-331007) (SOF-007) in human plasma of patients infected with HCV having ESRD using an optimized liquid chromatography-mass spectrometry (LC-MS) analytical method.

In this case-control study, 10 clinically confirmed cases and five controls were enrolled. SOF-007 was extracted from plasma using methanol precipitation. The limit of detection (LOD) for the drug and its metabolite were 0.85 and 2.3, respectively. Such a wide range of quantification in a period of separation time shorter than 3.0 minutes (run time) allowed monitoring of the plasma concentration of analytes up to 4 hours (pre-dialysis and post-dialysis) for 12 weeks in non-cirrhotic patients with HCV infection undergoing dialysis.

SOF-007 in the plasma of HCV patients with healthy kidneys showed no cumulative effect. An analysis comparing patients with ESRD and healthy participants showed that their behaviour was similar, followed by dialysis with a relatively small cumulative effect.

The plasma concentrations of SOF-007 decreased significantly after the 4-hour period of dialysis compared with the plasma concentrations hemodialysis of pre-dialysis in HCV patients with ESRD.

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