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

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

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.

• Jezik: Angleški jezik
• Ključne besede: impurities, degradation, phenyls, chromatography, solvents
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FFA - Fakulteta za farmacijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2022
• Št. strani: Str. 8896–8905
• Številčenje: Vol. 7, iss. 10
• PID: 20.500.12556/RUL-140522
• UDK: 542.61+543.544:615
• ISSN pri članku: 2470-1343
• DOI: 10.1021/acsomega.1c07260
• COBISS.SI-ID: 100925955
• Datum objave v RUL: 15.09.2022

Gradivo je del revije

• Naslov: ACS omega
• Skrajšan naslov: ACS omega
• Založnik: American Chemical Society
• ISSN: 2470-1343
• COBISS.SI-ID: 525873945

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: nečistoče, razgradnja, fenili, kromatografija, zdravila, topila

Projekti

• Financer: Drugi - Drug financer ali več financerjev
• Program financ.: Lek/Sandoz