title: Validated stability-indicating HPLC-DAD method for determination of the recently approved hepatitis C antiviral agent daclatasvir.
abstract: A comprehensive stability indicating HPLC with diode array detection method was developed for the determination of the recently approved antiviral drug daclatasvir dihydrochloride (DCV) which is used for the treatment of chronic Hepatitis C Virus (HCV) genotype 3 infection. Effective chromatographic separation was achieved using Waters C8 column (4.6×250mm, 5μm particle size) with isocratic elution of the mobile phase composed of mixed phosphate buffer pH 2.5 and acetonitrile in the ratio of 75:25 (by volume). The mobile phase was pumped at a flow rate of 1.2mL/min, and quantification of DCV was based on measuring its peak areas at 306nm. DCV eluted at retention time 5.4min. Analytical performance of the proposed HPLC procedure was thoroughly validated with respect to system suitability, linearity, range, precision, accuracy, specificity, robustness, detection and quantification limits. The linearity range was 0.6-60μg/mL with correlation coefficient>0.99999. The drug was subjected to forced degradation conditions of neutral, acidic and alkaline hydrolysis, oxidation and thermal degradation. The proposed method proved to be stability-indicating by resolution of the drug from its forced-degradation products. The validated HPLC method was successfully applied to analysis of the cited drug in its tablets.
authors.affiliation: Methodology Department, Pharco Pharmaceuticals Company, Alexandria, Egypt.
authors.forename: M M
authors.initials: MM
authors.lastname: Baker
authors.affiliation: Pharmaceutical Chemistry Department, Faculty of Pharmacy, University of Alexandria, Elmessalah, 21521 Alexandria, Egypt.
authors.forename: D S
authors.initials: DS
authors.lastname: El-Kafrawy
authors.affiliation: Pharmaceutical Chemistry Department, Faculty of Pharmacy, University of Alexandria, Elmessalah, 21521 Alexandria, Egypt.
authors.forename: M S
authors.initials: MS
authors.lastname: Mahrous
authors.affiliation: Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, University of Alexandria, Elmessalah, 21521 Alexandria, Egypt. Electronic address: tbelaleg@yahoo.com.
authors.forename: T S
authors.initials: TS
authors.lastname: Belal
mesh_terms: D000998:Antiviral Agents / Q000032:analysis*; D002219:Carbamates; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D006526:Hepatitis C / Q000188:drug therapy*; D007093:Imidazoles / Q000032:analysis*; D057230:Limit of Detection; D019999:Pharmaceutical Solutions; D011759:Pyrrolidines; D015203:Reproducibility of Results; D013607:Tablets; D014633:Valine / Q000031:analogs & derivatives
chemical_list: D000998:Antiviral Agents; D002219:Carbamates; D007093:Imidazoles; D019999:Pharmaceutical Solutions; D011759:Pyrrolidines; D013607:Tablets; D014633:Valine; C549273:daclatasvir
keywords: CLHP; Daclatasvir; Diode array detection; Dégradation forcée; Détection barette de diode; Forced degradation; HCV; HPLC; Methode indicatrice de stabilité; Stability-indicating assay