Abstract
Objective: The objective of this study was to report the stability of antiviral drug, daclatasvir (DCV) based on the information obtained from forced degradation studies and characterization of degradation products (DPs) by tandem mass spectrometry (MS/MS) analysis.
 Methods: Chromatographic separation was achieved on Shimadzu liquid chromatography (LC) 20 AD high-performance LC system with photodiode array detector having Kromasil C18 (250 mm×4.6 mm×5 μm) with isocratic elution of a mobile phase composed of ammonium acetate buffer (pH 4.5) and acetonitrile in a ratio of 50:50 at 315 nm. The drug was subjected to forced hydrolytic, oxidative, photolytic, and thermal stress in accordance with the ICH guideline Q1A (R2). The drug showed degradation under acidic and basic hydrolytic conditions by forming two DPs. The DPs were characterized using LC– MS/MS studies and the pathways of fragmentation are proposed. Validation of the developed method was carried out in accordance with ICH guidelines.
 Results: Two DPs were identified, DP-1 as (S)-1-((S)-2-(5-(4’-(2-((S)-1-((S)-2-((methoxycarbonyl)amino)-3-methylbutanoyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)-[1,1’-biphenyl]-4-yl)-1H-imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-aminium and DP-2 as (S)-2-(5-(4’-(2-((S)-1-((S)-2- ((methoxycarbonyl)amino)-3-methylbutanoyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)-[1,1’-biphenyl]-4-yl)-1H-imidazol-2-yl)pyrrolidin-1-ium.
 Conclusion: The method proved to be simple, accurate, precise, specific, robust, and less time consuming and can be applied for the determination of DCV in bulk and marketed formulation.
Highlights
The quality of the drugs comprehends the potency, uniformity, purity, pharmacological action, stability, etc
The ICH guidelines on impurities [3] require characterization of all degradation products (DPs) formed in drug products at ≥0.1%
As DPs generated during storage may be at very low levels (~0.1–0.5%, w/w), stress studies are suggested to generate them in higher amounts [4]
Summary
Chromatographic separation was achieved on Shimadzu liquid chromatography (LC) 20 AD high-performance LC system with photodiode array detector having Kromasil C18 (250 mm×4.6 mm×5 μm) with isocratic elution of a mobile phase composed of ammonium acetate buffer (pH 4.5) and acetonitrile in a ratio of 50:50 at 315 nm. The drug was subjected to forced hydrolytic, oxidative, photolytic, and thermal stress in accordance with the ICH guideline Q1A (R2). The drug showed degradation under acidic and basic hydrolytic conditions by forming two DPs. The DPs were characterized using LC– MS/MS studies and the pathways of fragmentation are proposed. Validation of the developed method was carried out in accordance with ICH guidelines
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