20.500.12556/RUL-133869 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 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. AQbD UHPLC method development method optimization design of experiments pharmacopeia ropinirole hydrochloride farmacevtska kemija farmakopeja true false true Angleški jezik Slovenski jezik Članek v reviji 2021-12-17 14:39:20 2021-12-17 14:39:27 2022-09-13 03:52:51 0000-00-00 00:00:00 2020 0 0 20 str. iss. 11, art. 2691 Vol. 25 2020 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 615.4:615.11:54 1420-3049 10.3390/molecules25112691 19106563 RAZ_Tome_Tim_2020.pdf RAZ_Tome_Tim_2020.pdf 1 8BCCA261012968BF523C12BE46B40434 4322bcf188fbcd66b88f11c47522598937f3c53e687b6d549a382a043a1bc5ce e93c20c1-5f3e-11ec-abdb-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=152231 https://www.mdpi.com/1420-3049/25/11/2691 0 a0543554-5f3e-11ec-abdb-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=152230 Fakulteta za farmacijo 0 0 0