针对患有肾上腺皮质癌的患者中甲氧嘧啶及其代谢物对映异构体的分析表明存在对映选择性代谢的二维色谱方法。
Two-dimensional chromatography for enantiomeric analysis of mitotane and its metabolite o,p'-DDA in patients with adrenocortical carcinoma indicates enantioselective metabolism.
发表日期：2023 Sep 03
作者：
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
来源：
BIOORGANIC CHEMISTRY
摘要：
曲安奈是一种手性药物，用于治疗肾上腺皮质癌，会被代谢为o,p'-二氯二苯乙酸（o,p'-DDA），同样是一种手性化合物。尽管具有重要的治疗意义，但其整体比例和对映异构体一直不为人所知。在本研究中，我们采用新开发的二维色谱技术中的手性相方法，分析了患者血浆中曲安奈和o,p'-DDA的对映异构体。在（S）/（R）-曲安奈比例方面观察到了重要差异，从1:1.2到1:10不等，而（S）/（R）-o,p'-DDA比例相对保持在约为2:1。这些发现为对映选择性代谢提供了证据，并提供了进一步分析曲安奈和代谢产物的方法，可以解释治疗反应的变异。版权所有© 2023 Elsevier Inc. 保留所有权利。
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.Copyright © 2023 Elsevier Inc. All rights reserved.