Abstract |
Mitotane is a chiral drug used to treat adrenocortical carcinoma, being metabolized to the o,p'-dichlorodiphenyl acetic acid ( o,p'-DDA), also a chiral compound. Despite of its therapeutic significance, the overall ratios and enantiomers have not been known. In this study, we analyzed the enantiomers of mitotane and o,p'-DDA in the plasma of patients by a newly developed chiral-phase method employed in two-dimensional chromatography. Important differences were observed in the ratio of (S)/(R)- mitotane, which varied substantially from 1:1.2 to 1:10 whereas the (S)/(R)- o,p'-DDA ratio was relatively conserved, at approximately 2:1. These findings provide evidence for the enantioselective metabolism and provide a method for further analyses of mitotane and metabolites, which can explain the variation in the therapeutic response.
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Authors | Gabriela Stadler, Alan de Almeida Veiga, Claudia Rita Corso, Camila Bach de Assis, Beatriz de Toledo Nogueira, Lucia Regina Rocha Martins, Beatriz Cruz Bonk, Flávia Lada Degaut Pontes, Bonald Cavalcante de Figueiredo, Lauro Mera de Souza |
Journal | Bioorganic chemistry
(Bioorg Chem)
Vol. 141
Pg. 106835
(12 2023)
ISSN: 1090-2120 [Electronic] United States |
PMID | 37713949
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2023 Elsevier Inc. All rights reserved. |
Chemical References |
- 2,2-(2-chlorophenyl-4'-chlorophenyl)acetic acid
- Mitotane
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Topics |
- Humans
- Mitotane
(therapeutic use, metabolism)
- Adrenocortical Carcinoma
(drug therapy)
- Stereoisomerism
- Chromatography, High Pressure Liquid
(methods)
- Adrenal Cortex Neoplasms
(drug therapy, metabolism)
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