Abstract
An isocratic stability-indicating reversed phase high performance liquid chromatographic method (RP-HPLC) was developed for determination of process related impurities and assay of darifenacin hydrobromide (DRF) in bulk drugs. DRF was subjected to various stress conditions such as hydrolysis (acid, base, and neutral), oxidation, photolysis and thermal degradation as per International Conference on Harmonization (ICH Q1A(R2) and Q1B) prescribed conditions to investigate the stability-indicating ability of the method. Significant degradation was observed during acidic hydrolysis and oxidative stress conditions. The chromatographic separation was accomplished on a Prodigy C8 column (250 × 4.6 mm, 5 μm) with mobile phase consisting of 0.05 M ammonium acetate (pH adjusted to 7.2 by using ammonia solution) and methanol (36% acetonitrile) in 35:65 v/v ratio in an isocratic elution mode at a flow rate of 1.0 mL/min at 25°C. Detection of analytes was carried out using photo diode array detector at a wavelength of 215 nm. The developed LC method was validated with respect to accuracy, linearity, precision, limits of detection and quantitation and robustness as per ICH guidelines.
Highlights
Darifenacin hydrobromide (DRF), a novel antimuscarinic agent, chemically known as (S)-2-[1-[2-(2,3-dihydrobenzofuran-5-yl)ethyl] pyrrolidin-3-yl]-2,2-diphenyl-acetamide hydrobromide, is a medication used to treat overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency
The main objective of the development of a chromatographic method was to get the good separation of impurities and stress degradation products from DRF and each other
In the initial stages of method development with C18 stationary phase columns (Agilents’ XDB and Extend) showed very quick elution of Imp-1 and DRF along with peak asymmetry with several mobile phase compositions consisting of acetate/ phosphate buffers and acetonitrile/methanol due to their high polarity
Summary
Darifenacin hydrobromide (DRF), a novel antimuscarinic agent, chemically known as (S)-2-[1-[2-(2,3-dihydrobenzofuran-5-yl)ethyl] pyrrolidin-3-yl]-2,2-diphenyl-acetamide hydrobromide, is a medication used to treat overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency It works by blocking the M3 muscarinic acetylcholine receptor selectively, which is primarily responsible for bladder contractions, thereby decreases the urgency to urinate [1] [2]. S. Thomas et al reported a selective stability-indicating HPLC method for DRF in the presence of process related impurities and stress degradation products and characterization of degradation products by LC-MS studies [3]. To the best of our knowledge, no rapid stability-indicating HPLC method for the quantitative determination of DRF in drug substance in presence of more susceptible process related impurities in bulk drugs was reported
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