A Stability-Indicating UPLC Method for the Determination of Potential Impurities and Its Mass by a New QDa Mass Detector in Daclatasvir Drug Used to Treat Hepatitis C Infection

Abstract

A stability-indicating ultraperformance liquid chromatographic method has been developed for the quantitative determination of degradation products and process-related impurities of daclatasvir in a pharmaceutical dosage form. Chromatographic separation was achieved on a polar Waters ACQUITY BEH phenyl 100 × 2.1 mm, 1.7-μm column using the gradient program consisting of mobile phase A: 0.03 M sodium perchlorate with 0.002 M of 1-octanesulfonic acid sodium salt (pH 2.5 buffer) and mobile phase B: 0.03 M sodium perchlorate with 0.02 M of 1-octanesulfonic acid sodium salt (pH 2.5 buffer) with acetonitrile in the ratio of 20:80% v/v. A flow rate of 0.4 mL/min is maintained under ultraviolet detection at 305 nm. The run time was 15 min, within which daclatasvir, its related impurities and unknown degradants were well resolved. The method was found to produce symmetric and sharp peaks with good separation between process-related impurities and degradation impurities. Samples were subjected to hydrolysis (acid and base), oxidative, photolytic and thermal stress conditions to prove the stability-indicating nature of the method. The unknown degradation products were identified by PDA/QDa mass detector. This mass spectrum reveals protonated molecular ion peaks [M + H]+ at m/z DP1-582.4 in acid and base hydrolyses and m/z DP2-778.5 in peroxide hydrolysis. The method was validated in terms of specificity, precision, linearity, accuracy, limit of detection, limit of quantification and robustness as per ICH guidelines.

Liver Targeting of Daclatasvir via Tailoring Sterically Stabilized Bilosomes: Fabrication, Comparative In Vitro/In Vivo Appraisal and Biodistribution Studies

“… 4 DAC is said to be a biopharmaceutical classification system class II compound (low solubility/high permeability). 4 …”

“…3 A new direct-acting antiviral drug, daclatasvir (DAC), is approved for use in over 60 countries around the world for treating HCV infection in adults 3 as it has a rapid declining effect on HCV-RNA, where it targets two steps in the process of viral replication by inhibiting HCV non-structural protein NS5A. 4 DAC is said to be a biopharmaceutical classification system class II compound (low solubility/high permeability). 4 The major problems with standard pharmacological treatment are the inability to deliver a sufficient amount of active therapeutic agent to the diseased liver and the undesirable systemic effects.…”

Applying different spectroscopic techniques for the selective determination of daclatasvir using merbromin as a probe: Applications on pharmaceutical analysis

“…[ 4,5,7 ] In addition, daclatasvir dihydrochloride has been determined using chromatographic techniques combined with different detection patterns. [ 12–16 ] Generally, chromatographic methodologies require a large volume of hazardous organic solvents, tedious procedures, long time periods, and expensive detectors. Merbromin or sodium mercurescein is a stable low‐cost fluorescent reagent [ 17 ] and has been applied spectrophotometrically and fluorometrically for the quantification of some antibiotics, fluoroquinolones, thio‐compounds, dapoxetine hydrochloride, and allopurinol in their pharmaceutical dosage forms.…”

Stability indicating HPLC-Fluorescence detection method for the simultaneous determination of linagliptin and empagliflozin in their combined pharmaceutical preparation

“…Literature surveys released several analytical designs that have been established for the determination of both LNG and EMP mixtures in dosage forms and biological fluids; these methods include chromatographic [4][5][6][7][8][9][10][11][12][13][14][15][16][17], spectrophotometric methods [18][19][20][21], spectroflourimetric method [22] and electrochemical method [23].…”