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Two-dimensional chromatography for enantiomeric analysis of mitotane and its metabolite o,p′-DDA in patients with adrenocortical carcinoma indicates enantioselective metabolism
A 2D-LC method was developed to quantify the enantiomers of mitotane and its metabolite, o,p′-DDA modified to n-Propyl ester, revealing that mitotane undergoes enantioselective metabolism. [Display omitted] •A new chromatography was developed for chiral mitotane and its metabolite monitoring.•Mitota...
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Published in: | Bioorganic chemistry 2023-12, Vol.141, p.106835-106835, Article 106835 |
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Main Authors: | , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites |
Online Access: | Get full text |
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Summary: | A 2D-LC method was developed to quantify the enantiomers of mitotane and its metabolite, o,p′-DDA modified to n-Propyl ester, revealing that mitotane undergoes enantioselective metabolism.
[Display omitted]
•A new chromatography was developed for chiral mitotane and its metabolite monitoring.•Mitotane undergoes a chiral-oriented metabolism, observed in the ratio of enantiomers.•The ratio of mitotane to metabolites varies greatly between different patients.
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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ISSN: | 0045-2068 1090-2120 |
DOI: | 10.1016/j.bioorg.2023.106835 |