New insights for screening etomidate analogues in the human H295R cell model.

Etomidate is a sedative-hypnotic with excellent pharmacological effects, including rapid onset and hemodynamic stability. However, etomidate causes adrenocortical toxicity via binding to 11β-hydroxylase. Therefore, developing an approach to screen new etomidate analogues without endocrine-disrupting effects is urgently warranted. In this study, we employed the adrenocortical tumour cell line, NCI-H295R, as an in vitro system for etomidate analogues screening and detected the hormone levels in these cells using a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method. After obtaining the concentration-response curves of hormone release, the "Adrenocortical Inhibitory Index" was used to evaluate the adrenocortical inhibitory potency of each compound. In summary, we demonstrate the benefits of our methods for screening of etomidate analogues that lack adrenocortical suppression, especially when this in vitro system is combined with in vivo testing. • H295R assay would serve as a good in vitro system for etomidate analogs screening. • AII may be used as a preliminary evaluation criterion for adrenocortical toxicity. • An in vitro system may predict adrenocortical inhibition in vivo. [ABSTRACT FROM AUTHOR]