Unique Quality by Design Approach for Developing HPLC and LC-MS Method for Estimation of Process and Degradation Impurities in Pibrentasvir, Antiviral Agent for Hepatitis C

Abstract

Pibrentasvir (PIB) was approved for treating hepatitis C patients. A specific, accurate, linear, robust, and stability-indicating method was developed and validated for determining degradation impurities present in the PIB drug substance by studying the quality by design (QbD) principles. All identified degradation impurities were separated with the stationary phase HALO C18, 150 mm × 4.6 mm, 2.7 μm. Mobile phase A contains pH 2.5 phosphate buffer and acetonitrile in the ratio of (70:30, v/v), and mobile phase B contains water and acetonitrile in the ratio of (30:70, v/v), respectively. The chromatographic conditions were optimized, such as flow rate of 0.8 mL/min, UV detection at 252 nm, injection volume of 20 μL, and column temperature of 40 °C. The proposed method was validated per the current ICH Q2 (R1) guidelines. The recovery study and linearity ranges were established from limit of quantification (LOQ) to 300% optimal concentrations. The method validation results were between 98.6% and 106.2% for recovery, and linearity r 2 was more than 0.999 for all identified impurities. The method precision results achieved below 5% relative standard deviation (RSD). The forced degradation results demonstrated that the drug was sensitive to chemical stress conditions. During the stress study, degrading impurities were identified by the LC-MS technique and the mechanism pathway. A QbD-based experimental design (DoE) approach was used to establish the robustness of the method.

Quality by design tool–evaluated stability‐indicating ultra‐performance liquid chromatography method for the determination of drugs (ritonavir and darunavir) used to treat the human immunodeficiency virus/acquired immunodeficiency syndrome

“…In general, the technique should be enhanced or its robustness should be proven using the quality by design (QbD) approach, according to the present regulatory criteria, which are unambiguous. The robustness of the recently presented strategy was demonstrated using the QbD tool (Dandabattina et al, 2023; Jythesh Kumar et al, 2023; Konduru et al, 2022; Kowtharapu et al, 2022; Vemuri et al, 2022). The design of experiments based on QbD were carried out using Design‐Expert software version 13 (Stat‐Ease, Inc., Minneapolis, MN).…”