Development of a unified reversed-phase HPLC method for efficient determination of EP and USP process-related impurities in celecoxib using analytical quality by design principles

Tome, Tim (author), Časar, Zdenko (author), Obreza, Aleš (author)

This article presents the development of a reversed-phase (RP) high-performance liquid chromatographic (HPLC) method for determination of process-related impurities in a celecoxib drug substance following Analytical Quality by Design (AQbD) principles. The method from European Pharmacopeia (EP) for celecoxib drug substance does not sufficiently separate celecoxib from its EP impurity B because the system suitability criterion is not achieved (resolution NLT 1.8). The same issue was observed with the proposed method from United States Pharmacopeia (USP) for celecoxib capsules, where EP impurity A elutes under the main peak. A new HPLC method was developed that eliminates the disadvantages of the two pharmacopeial methods and is capable of efficiently separating and determining all seven impurities listed in EP and the proposed USP monographs. The development of a new HPLC method started with method scouting, in which various C18 and phenyl stationary phases were tested. Improved selectivity was obtained only with a chiral stationary phase. An immobilized Chiralpak IA-3 column used in RP mode turned out to be the most appropriate for method optimization. The ratio of acetonitrile in the mobile phase, flow rate, and column temperature were recognized as critical method parameters (CMPs) and were further investigated using a central composite face response-surface design. A multiple linear regression (MLR) method was applied to fit the mathematical models on the experimental data to determine factor–response relationships. The models created show adequate fit and good prediction abilities. The Monte Carlo simulation method was used to establish the design space. The method developed was verified in terms of precision, sensitivity, accuracy, and linearity, and the results showed that the new method is suitable for determination of seven process-related impurities of celecoxib.

• Language: English
• Keywords: RP-HPLC, AQbD, HPLC method development, HPLC method optimization, pharmacopeia, celecoxib
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2020
• Number of pages: 18 str.
• Numbering: Vol. 25, iss. 4, art. 809
• PID: 20.500.12556/RUL-133205
• UDC: 543.544.5:615.11:54
• ISSN on article: 1420-3049
• DOI: 10.3390/molecules25040809
• COBISS.SI-ID: 4882289
• Publication date in RUL: 17.11.2021

Record is a part of a journal

• Title: Molecules
• Shortened title: Molecules
• Publisher: MDPI
• ISSN: 1420-3049
• COBISS.SI-ID: 18462981

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
• Licensing start date: 13.02.2020

Secondary language

• Language: Slovenian
• Keywords: celekoksib, farmakopeja, tekočinska kromatografija, farmacevtska kemija