Developing an Improved UHPLC Method for Efficient Determination of European Pharmacopeia Process-Related Impurities in Ropinirole Hydrochloride Using Analytical Quality by Design Principles

This article presents the development of a reversed-phase ultra-high-performance liquid chromatographic method for determining process-related impurities in ropinirole hydrochloride drug substance applying the analytical quality by design approach. The current pharmacopeial method suffers from selec...

Full description

Saved in:
Bibliographic Details
Published in:Molecules (Basel, Switzerland) Switzerland), 2020-06, Vol.25 (11), p.2691
Main Authors: Tome, Tim, Obreza, Aleš, Časar, Zdenko
Format: Article
Language:English
Subjects:
AQbD
Chromatography
Chromatography, High Pressure Liquid - methods
Design
Design analysis
design of experiments
Drug Contamination - statistics & numerical data
Drug development
Elution
Experiments
Impurities
Indoles - analysis
Indoles - chemistry
Limit of Detection
Linearity
Mathematical models
method development
method optimization
Methods
Models, Theoretical
Pharmacology
pharmacopeia
Quality Control
Reproducibility of Results
Restless legs syndrome
Selectivity
Slope gradients
UHPLC
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:This article presents the development of a reversed-phase ultra-high-performance liquid chromatographic method for determining process-related impurities in ropinirole hydrochloride drug substance applying the analytical quality by design approach. The current pharmacopeial method suffers from selectivity issues due to two coelutions of two pairs of impurities. The development of a new method began with preliminary experiments, based on which the Acquity UPLC BEH C8 was selected as the most appropriate column. The effects of six different critical method parameters (CMPs) were then investigated using a fractional factorial screening design. Column temperature, the ratio of methanol in mobile phase B, and gradient slope turned out to be highly significant CMPs in achieving critical resolutions, and they were further evaluated using a central composite face-centered response-surface design. Mathematical models were created by applying a multiple linear regression method. Based on the elution order of an unknown degradation impurity and impurity C, two design spaces were established, and for each design space an optimal combination of CMPs was determined. The method developed was validated for precision, accuracy, linearity, and sensitivity, and it was proven suitable for determining nine process-related impurities of ropinirole.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules25112691