Development of an analytical method for determination of related substances and degradation products of cabotegravir using analytical quality by design principles

Kovač, Lidija (author), Časar, Zdenko (author), Trdan Lušin, Tina (author), Roškar, Robert (author)

Cabotegravir is one of the newly approved human immunodeficiency virus (HIV) integrase enzyme inhibitors used for the prevention and treatment of HIV infection. It is the first approved long-acting injectable antiretroviral therapy for HIV and is also very effective in combination with rilpivirine, a non-nucleoside reverse transcriptase inhibitor. Therefore, future drug development involving cabotegravir can be expected. We developed an ultrahigh performance liquid chromatography (UHPLC) method compatible with mass spectrometry for the determination of eight cabotegravir impurities. The described method is able to differentiate cabotegravir and its related substances as well as its degradation products. Analytical quality by design principles were used for method development. The method is robust within the defined method operable design region: flow rate = 0.32–0.40 mL/min; column temperature = 30–40 °C; pH of mobile phase A = 3.25–3.75, and the final percent of acetonitrile in gradient = 50.0–60.0%. Inside the method operable design region, a working optimal point was selected: pump flow rate = 0.36 mL/min; column temperature = 35 °C; pH of mobile phase A = 3.5, and final percent of acetonitrile in gradient = 55%. Method validation was performed, and the following parameters were verified: accuracy, repeatability, linearity, response factors, detection limit, and quantification limit. All method validation results were within selected criteria. The presented method could be used for the development of new pharmaceutical products based on cabotegravir.

• Language: English
• Keywords: impurities, degradation, phenyls, chromatography, solvents
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2022
• Number of pages: Str. 8896–8905
• Numbering: Vol. 7, iss. 10
• PID: 20.500.12556/RUL-140522
• UDC: 542.61+543.544:615
• ISSN on article: 2470-1343
• DOI: 10.1021/acsomega.1c07260
• COBISS.SI-ID: 100925955
• Publication date in RUL: 15.09.2022

Record is a part of a journal

• Title: ACS omega
• Shortened title: ACS omega
• Publisher: American Chemical Society
• ISSN: 2470-1343
• COBISS.SI-ID: 525873945

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.

Secondary language

• Language: Slovenian
• Keywords: nečistoče, razgradnja, fenili, kromatografija, zdravila, topila

Projects

• Funder: Other - Other funder or multiple funders
• Funding programme: Lek/Sandoz