Abstract
BackgroundA novel gradient, high-sensitive and specific stability-indicating reverse-phase HPLC method was developed and validated for quantitative purpose of known, unknown and degradant impurities profiling for diltiazem hydrochloride tablets. The impurities were separated on the Zorbax RX C8 column (150 mm × 4.6 mm, 5 μm) with mobile phase-A consisting of a mixture of 0.05 M sodium dihydrogen phosphate monohydrate buffer pH 3.0 and methanol in the ratio 800:200v/v and mobile phase-B consisting of acetonitrile with a flow rate of 1.0 mL min−1. The column compartment was maintained at 35 °C, and the detection wavelength was 240 nm. Diltiazem hydrochloride, its known impurities and unknown impurities have been well resolved from each other.ResultsThe linearity of the method has been demonstrated across the concentration range of 0.18 to 5.65 µg mL−1 for EP impurity-F with correlation coefficient R2 greater than 0.99. Recovery of method was proved from LOQ to 150% for known and unknown impurities with respect to test concentration and found in between 80 and 120%. Forced degradation study and specificity experiment results with mass balance proved the stability-indicating nature of the method and separated all known, unknown impurities and degradants from each other as well as from main drug component (diltiazem hydrochloride). The mass balance for stress study was found in between 95 and 105%.ConclusionNewly developed analytical method was validated as per ICH Q2 (R1) guidelines “Validation of analytical procedure” and found linear, accurate, specific, robust and precise in the established working range.
Highlights
A novel gradient, high-sensitive and specific stability-indicating reverse-phase High-Performance Chromatography (HPLC) method was developed and validated for quantitative purpose of known, unknown and degradant impurities profiling for diltiazem hydrochloride tablets
Method validation The developed reverse-phase HPLC analytical method was validated according to ICH guidelines with respect to specificity, accuracy, precision, linearity, range and robustness
The acceptance criteria defined from six replicate injections of standard solution are %RSD of diltiazem peak area should not be more than 5.0%, USP tailing for diltiazem peak should not be more than 2.0 and USP plate count for diltiazem peak should not be less than 5000
Summary
A novel gradient, high-sensitive and specific stability-indicating reverse-phase HPLC method was developed and validated for quantitative purpose of known, unknown and degradant impurities profiling for diltiazem hydrochloride tablets. Forced degradation study and specificity experiment results with mass balance proved the stability-indicating nature of the method and separated all known, unknown impurities and degradants from each other as well as from main drug component (diltiazem hydrochloride). The drug product is considered safe when the levels of impurities (known and unknown) are below the maximum permeability limits during the shelf-life study according to ICH guidelines [4, 5]. The force degradation study will help identify unknown potential degradants and provide information necessary for the stability of drug substances and pharmaceutical products. The results of the diltiazem hydrochloride degradation study, which will provide information on the intrinsic stability of the drug product, are reported here
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
