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Despite the recent epidemic of fentanyl abuse, there are few validated assays capable of rapidly detecting these compounds. In order to improve the ability to detect carfentanil at physiologically relevant concentrations, we developed a systems biology approach to discover host-based markers which are specifically amplified upon exposure in a rabbit model. For this work, two "omics" pipelines utilizing mass spectrometry were developed and leveraged. First, a proteomics pipeline was developed to interrogate the blood plasma for protein-based biomarkers. Due to the incredible dynamic range of the plasma protein content, a multi-dimensional fractionation technique was used to partition and more accurately investigate the circulating plasma proteome. Isobaric tandem mass tags were integrated into the workflow to make quantitative assessments across all animals for an extended time course post-exposure. In addition to the proteomics efforts, blood plasma was also processed through an untargeted metabolomics pipeline. This approach allows for the identification of >800 small molecule features. By processing and analyzing data sets in parallel, we were able to identify a unique fingerprint of protein and metabolite perturbations that manifest following exposure to carfentanil. [ABSTRACT FROM AUTHOR]

Lewisite (Military Code: L) is an arsenical vesicant chemical warfare agent (CWA) that was developed in the United States during World War I. Even though its use has not been documented in warfare, large stockpiles were created and still exist in various locations around the world. Given that large quantities exist as well as the relative straightforward process for its creation, Lewisite still presents itself as a serious threat agent. In this study, we examined the effects of Lewisite on human dermal equivalent tissues (EpiDerm™/EpiDerm™-FT) through the evaluation of cellular viability, histology, and multiomic analysis., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Elizabeth Dhummakupt reports financial support was provided by Defense Threat Reduction Agency. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)