Development of an Analytical Method for Determination
of Related Substances and Degradation Products of Cabotegravir Using
Analytical Quality by Design Principles
posted on 2022-03-04, 20:04authored byLidija Kovač, Zdenko Časar, Tina Trdan Lušin, Robert Roškar
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.