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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-06-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/11/2691 |
| _version_ | 1797565625066848256 |
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| author | Tim Tome Aleš Obreza Zdenko Časar |
| author_facet | Tim Tome Aleš Obreza Zdenko Časar |
| author_sort | Tim Tome |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T19:15:46Z |
| format | Article |
| id | doaj.art-284e149946dc46cc8882c5bcda5614f1 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T19:15:46Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-284e149946dc46cc8882c5bcda5614f12023-11-20T03:24:29ZengMDPI AGMolecules1420-30492020-06-012511269110.3390/molecules25112691Developing an Improved UHPLC Method for Efficient Determination of European Pharmacopeia Process-Related Impurities in Ropinirole Hydrochloride Using Analytical Quality by Design PrinciplesTim Tome0Aleš Obreza1Zdenko Časar2Faculty of Pharmacy, University of Ljubljana, Aškerčeva c. 7, Ljubljana SI-1000, SloveniaFaculty of Pharmacy, University of Ljubljana, Aškerčeva c. 7, Ljubljana SI-1000, SloveniaFaculty of Pharmacy, University of Ljubljana, Aškerčeva c. 7, Ljubljana SI-1000, SloveniaThis 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.https://www.mdpi.com/1420-3049/25/11/2691AQbDUHPLCmethod developmentmethod optimizationdesign of experimentspharmacopeia |
| spellingShingle | Tim Tome Aleš Obreza Zdenko Časar Developing an Improved UHPLC Method for Efficient Determination of European Pharmacopeia Process-Related Impurities in Ropinirole Hydrochloride Using Analytical Quality by Design Principles Molecules AQbD UHPLC method development method optimization design of experiments pharmacopeia |
| title | Developing an Improved UHPLC Method for Efficient Determination of European Pharmacopeia Process-Related Impurities in Ropinirole Hydrochloride Using Analytical Quality by Design Principles |
| title_full | Developing an Improved UHPLC Method for Efficient Determination of European Pharmacopeia Process-Related Impurities in Ropinirole Hydrochloride Using Analytical Quality by Design Principles |
| title_fullStr | Developing an Improved UHPLC Method for Efficient Determination of European Pharmacopeia Process-Related Impurities in Ropinirole Hydrochloride Using Analytical Quality by Design Principles |
| title_full_unstemmed | Developing an Improved UHPLC Method for Efficient Determination of European Pharmacopeia Process-Related Impurities in Ropinirole Hydrochloride Using Analytical Quality by Design Principles |
| title_short | Developing an Improved UHPLC Method for Efficient Determination of European Pharmacopeia Process-Related Impurities in Ropinirole Hydrochloride Using Analytical Quality by Design Principles |
| title_sort | developing an improved uhplc method for efficient determination of european pharmacopeia process related impurities in ropinirole hydrochloride using analytical quality by design principles |
| topic | AQbD UHPLC method development method optimization design of experiments pharmacopeia |
| url | https://www.mdpi.com/1420-3049/25/11/2691 |
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