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Development and Validation of a New LC–MS/MS Analytical Method for Direct-Acting Antivirals and Its Application in End-Stage Renal Disease Patients

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Abstract

Background and Objective

The effectiveness of direct-acting antivirals (DAAs) is not well established in end-stage renal disease (ESRD) patients. Assessment of the plasma concentrations may support understanding of their therapeutic outcomes in this population. The aim of this study is to develop a direct, yet matrix-effect tolerant, analytical method for determining DAAs in the plasma of ESRD patients while maintaining a moderate cost per sample and with an improved analyte extraction recovery.

Methods

In this study, a liquid chromatography–tandem mass spectrometric (LC–MS/MS) method was developed for the analysis of ombitasvir (OMB), paritaprevir (PRT) and ritonavir (RIT) in plasma. Sample preparation was performed using the liquid–liquid extraction (LLE) method. Isocratic separation was performed using a mixture of methanol and 10 mM ammonium acetate (79:21, v/v) followed by MS/MS detection. The method was validated and applied to determine DAAs in the plasma of ESRD patients (n = 7).

Results

The developed method was linear (r2 > 0.995), accurate (89.4 ± 7.8 to 108.3 ± 3.0) and precise (% CV 0.9–15.0) and showed improved recovery (> 80) over previously published ones in the range 5–250, 30–1,500, 20–1,000 ng/mL for OMB, PRT and RIT, respectively. Relative matrix effect was absent, and the method accurately determined the three DAAs in real-life samples (n = 7).

Conclusions

An efficient analytical method for the determination of DAAs is presented. The method overcomes the potential analytical response fluctuation in ESRD. The developed method show improved extraction recoveries and is suitable for routine application in developing economies where hepatitis C virus is most prevalent.

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Acknowledgements

The authors thank Professor Wilfried Niessen (hyphen MassSpec, Margrietstraat 34, 2215 HJ Voorhout, the Netherlands) for his appreciated efforts in revising this manuscript.

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Authors and Affiliations

  1. Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ahram Canadian University, 6th October City, Egypt

    Faten Farouk

  2. National Organization of Drug Quality Control and Research, Giza, Egypt

    Dina Wahba

  3. Internal Medicine Department, Hepato-gastroenterology Unit, Faculty of Medicine, Cairo University, Giza, Egypt

    Sherif Mogawer, Shaimaa Elkholy & Ahmed Elmeligui

  4. Internal Medicine Department, Nephrology Unit, Faculty of Medicine, Cairo University, Giza, Egypt

    Reham Abdelghani & Salwa Ibahim

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  1. Faten Farouk
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Correspondence to Faten Farouk.

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This study did not receive any funding.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Study was approved by the ethics committee of Cairo University; Faculty of Medicine; 2016.

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Informed consent was obtained from all individual participants included in the study.

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Farouk, F., Wahba, D., Mogawer, S. et al. Development and Validation of a New LC–MS/MS Analytical Method for Direct-Acting Antivirals and Its Application in End-Stage Renal Disease Patients. Eur J Drug Metab Pharmacokinet 45, 89–99 (2020). https://doi.org/10.1007/s13318-019-00584-6

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