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ISSN 2410-7751 (Print)
ISSN 2410-776X (Online)

 

Biotechnologia Acta  Т. 15, No. 1, 2022
P. 43-51. Bibliography 29, Engl.
UDC: 615.214.22.015.11
https://doi.org/10.15407/biotech15.01.043

METABOLIC PROFILE AND MECHANISMS OF GABA-TARGETED RECEPTOR PROPOXAZEPAM METABOLIZATION IN HUMAN HEPATOCYTES

 M. Golovenko 1, A. Reder 2, V. Larionov 1, S. Andronati 1

1 Physico-Chemical Institute of the National Academy of Sciences of Ukraine, Odesa
2 SLC «INTERCHEM», Odesa, Ukraine

The aim of this study was to identify the Propoxazepam metabolites, formed by suspension of cryopreserved human hepatocytes, using the precise method of mass LC-MS/MS analysis.

Methods. A suitable chromatographic method was developed for the profiling of Propoxazepam and its metabolites. Samples were analyzed using a Waters Vion high resolution LC-MS/MS instrument, and data were examined using Waters Unifi software to determine the identity of the most abundant metabolites. Following a 4-hour incubation with human hepatocytes, intact Propoxazepam molecule accounted for 96.0% of the profile. Its most abundant metabolite was the oxidize.

Results. Propoxazepam (3-hydroxyderivative), which accounted for approximately 2.5% of the total peak response in the 4-hour sample. Two minor components were also found, each accounting for < 10% of the total peak response. Glucuronic conjugates have not been found under the experimental conditions. All metabolites formed represented less than 10% of the total chromatographic peak response.

Coclusion. The data obtained indicate the absence of reactive electrophilic derivatives among the metabolites of Propoxazepam.

Key words: Propoxazepam, humanhepatocytes, metabolism, LC-MS/MS analysis.

© Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine, 2022