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RP-HPLC Stability Indicating Method Development and Validation for Simultaneous Determination of Grazoprevir and Elbasvir

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Abstract

Elbasvir (ELB) and grazoprevir (GZP) were two new approved drugs and their co-formulation presents one of the more recently approved combinations for treatment of hepatitis C virus. A stability indicating reversed phase-high performance liquid chromatography (RP-HPLC) method was developed for simultaneous determination of ELB and GZP and their degradation products under hydrolysis and oxidative stress conditions as per International Conference on Harmonization [ICH Q1A (R2) guidelines]. Adequate chromatographic separation with well-defined peaks was achieved using a Waters Spherisorb phenyl Column (150 mm × 4.6 mm I.D, 5 µm particle size) with a temperature maintained at 40 °C ± 2 °C. The mobile phase consists of acetonitrile: 5 mM ammonium formate buffer (+ 0.1% v/v of trimethylamin, pH was adjusted to 3.2 by formic acid) (60:40 v/v) at a flow rate of 0.8 mL min−1. A validation study was performed according to the accuracy profile methodology. Specificity, suitability, robustness, precision and trueness of the developed method were confirmed. The proposed method was also successfully compatible to identification of molecular structure of degradation products by liquid chromatography-mass spectrometry (LC–MS) coupling. A quadrupole-time of flight mass analyzer equipped with an electrospray ionization source was used to characterizing degradation products based on the MS spectra and accurate mass measurements.

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This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Faculté Des Sciences de Tunis, Laboratoire de Chimie Analytique Et Electrochimie, Université de Tunis El Manar, Campus Universitaire Farhat Hached, 2092, Tunis, Tunisia

    Aymen Labidi

  2. Laboratoire National de Contrôle Des Médicaments, 11 bis Rue Jebel Lakhdar Bab Saadoun, 1006, Tunis, Tunisia

    Aymen Labidi & Sami Jebali

  3. Laboratory of Materials, Treatment and Analysis, (LMTA), National Institute of Research and Physicochemical Analysis, Biotechpole Sidi-Thabet, Ariana, Tunisia

    Mehdi Safta

  4. Laboratoire de Chimie Minérale Appliquée (LR19ES02), Faculté Des Sciences de Tunis, Université de Tunis El Manar, Campus Universitaire Farhat Hached, 2092, Tunis, Tunisia

    Latifa Latrous El Atrache

  5. Institut Préparatoire Aux Etudes D’Ingénieurs D’El Manar, Université de Tunis El Manar, B.P. 244 El Manar II, 2092, Tunis, Tunisia

    Latifa Latrous El Atrache

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  1. Aymen Labidi
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  2. Sami Jebali
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Correspondence to Latifa Latrous El Atrache.

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The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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Labidi, A., Jebali, S., Safta, M. et al. RP-HPLC Stability Indicating Method Development and Validation for Simultaneous Determination of Grazoprevir and Elbasvir. Chemistry Africa 4, 607–619 (2021). https://doi.org/10.1007/s42250-021-00253-9

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  • DOI: https://doi.org/10.1007/s42250-021-00253-9

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