Establishing the metabolism pathway of the drug undergoing the hepatic biotransformation pathway is one of the most important aspects in the preclinical discovery process since the presence of toxic or reactive metabolites may result in drug withdrawal from the market. In this study, we present the structural elucidation of six, not described yet, metabolites of an antipsychotic molecule: molindone. The elucidation of metabolites was supported with a novel photocatalytical approach with the use of WO3 and WS2 assisted photochemical reactions. An UHPLC-ESI-Q-TOF combined system was used for the registration of all obtained metabolite profiles as well as to record the high resolution fragmentation spectra of the observed transformation products. As a reference in the in vitro metabolism simulation method, the incubation with human liver microsomes was used. Chemometric comparison of the obtained profiles pointed out the use of the WO3 approach as being more convenient in the field of dru...g metabolism studies. Moreover, the photocatalysis was used in the direction of the main drug metabolite synthesis in order to further isolation and characterization.
TY - JOUR
AU - Gawlik, Maciej
AU - Savić, Vladimir
AU - Jovanović, Miloš
AU - Skibiński, Robert
PY - 2020
UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3569
AB - Establishing the metabolism pathway of the drug undergoing the hepatic biotransformation pathway is one of the most important aspects in the preclinical discovery process since the presence of toxic or reactive metabolites may result in drug withdrawal from the market. In this study, we present the structural elucidation of six, not described yet, metabolites of an antipsychotic molecule: molindone. The elucidation of metabolites was supported with a novel photocatalytical approach with the use of WO3 and WS2 assisted photochemical reactions. An UHPLC-ESI-Q-TOF combined system was used for the registration of all obtained metabolite profiles as well as to record the high resolution fragmentation spectra of the observed transformation products. As a reference in the in vitro metabolism simulation method, the incubation with human liver microsomes was used. Chemometric comparison of the obtained profiles pointed out the use of the WO3 approach as being more convenient in the field of drug metabolism studies. Moreover, the photocatalysis was used in the direction of the main drug metabolite synthesis in order to further isolation and characterization.
PB - MDPI AG
T2 - Molecules
T1 - Mimicking of phase I metabolism reactions of molindone by HLM and photocatalytic methods with the use of UHPLC-MS/MS
VL - 25
IS - 6
DO - 10.3390/molecules25061367
ER -
@article{
author = "Gawlik, Maciej and Savić, Vladimir and Jovanović, Miloš and Skibiński, Robert",
year = "2020",
abstract = "Establishing the metabolism pathway of the drug undergoing the hepatic biotransformation pathway is one of the most important aspects in the preclinical discovery process since the presence of toxic or reactive metabolites may result in drug withdrawal from the market. In this study, we present the structural elucidation of six, not described yet, metabolites of an antipsychotic molecule: molindone. The elucidation of metabolites was supported with a novel photocatalytical approach with the use of WO3 and WS2 assisted photochemical reactions. An UHPLC-ESI-Q-TOF combined system was used for the registration of all obtained metabolite profiles as well as to record the high resolution fragmentation spectra of the observed transformation products. As a reference in the in vitro metabolism simulation method, the incubation with human liver microsomes was used. Chemometric comparison of the obtained profiles pointed out the use of the WO3 approach as being more convenient in the field of drug metabolism studies. Moreover, the photocatalysis was used in the direction of the main drug metabolite synthesis in order to further isolation and characterization.",
publisher = "MDPI AG",
journal = "Molecules",
title = "Mimicking of phase I metabolism reactions of molindone by HLM and photocatalytic methods with the use of UHPLC-MS/MS",
volume = "25",
number = "6",
doi = "10.3390/molecules25061367"
}
Gawlik, M., Savić, V., Jovanović, M.,& Skibiński, R.. (2020). Mimicking of phase I metabolism reactions of molindone by HLM and photocatalytic methods with the use of UHPLC-MS/MS. in Molecules
MDPI AG., 25(6).
https://doi.org/10.3390/molecules25061367
Gawlik M, Savić V, Jovanović M, Skibiński R. Mimicking of phase I metabolism reactions of molindone by HLM and photocatalytic methods with the use of UHPLC-MS/MS. in Molecules. 2020;25(6).
doi:10.3390/molecules25061367 .
Gawlik, Maciej, Savić, Vladimir, Jovanović, Miloš, Skibiński, Robert, "Mimicking of phase I metabolism reactions of molindone by HLM and photocatalytic methods with the use of UHPLC-MS/MS" in Molecules, 25, no. 6 (2020),
https://doi.org/10.3390/molecules25061367 . .
