Dear Colleagues,

The assessment of the potential toxicity of a new drug is critical during early phases of drug development as well in post-marketing surveillance. Investigation into the molecular events by which a drug causes injury is of utmost importance to improve drug safety. Metabolomics, a rapidly growing 'omic' that examines global changes in metabolite composition in cells and tissues, is a powerful tool that can be used to describe alterations caused by a drug in cells or tissues and to uncover its pathophysiological significance. Recent analytical and data analysis tools have made it possible and feasible to monitor metabolic alterations and cells’ responses to an injuring agent over a wide range of cells’ metabolites. On the basis of such analyses, it is possible to investigate global metabolome responses, discover altered outcome pathways, and uncover the mechanisms of toxicity involved to date. Based on the magnitude and relevance of metabolome changes induced in cells, tissues, or in vivo, it is also possible to discriminate between toxic and non-toxic compounds/concentrations. Toxicometabolomics analysis is the most closely related strategy to classical knowledge of disturbed biochemical pathways. It allows for the rapid identification of the potential targets of a hazardous compound and can also assist in the identification of potential toxic candidates in the early phases of drug discovery.

This Special Issue of Metabolites, entitled “Metabolomics in preclinical drug safety assessment”, aims to present the scope and applications of metabolomics in the early assessment of drug safety in the first stages of drug development, gathering  cutting-edge studies that explore and exemplify the use of metabolomics in different toxicological areas in vitro and in vivo. The issue is structured under several subheadings: Part A: general principles of metabolomic analysis and its application in drug safety assessment; Part B: metabolomics drug safety assessment in in vitro studies; Part C: in vivo metabolomic studies on drug safety; Part D: data quality assurance; Part E: metabolomic data analysis; and Part F: metabolomic data acceptance in the regulatory process.

We encourage the submission of original articles and reviews focused on these different subheadings and  addressing the following topics:

• General principles of metabolomics analysis for drug safety evaluation;
• Novel instrumental approaches in metabolomics analysis in early drug discovery;
• Metabolomics analysis in preclinical hepatotoxicity studies in vitro and in vivo;
• Metabolomics analysis in preclinical renal toxicity studies in vitro and in vivo;
• Metabolomics analysis in preclinical hematopoietic system toxicity studies in vitro and in vivo;
• Metabolomics analysis in preclinical neural toxicity studies in vitro and in vivo;
• Metabolomics analysis in preclinical cardiac toxicity studies  in vitro and in vivo;
• Quality assurance and GLPs in metabolomics;
• Metabolomics data analysis and metabolic pathways;
• General criteria for metabolomics data acceptance by drug regulatory agencies.

Articles may also address toxicity biomarker identification, metabolomics approaches to unraveling toxicity mechanisms and altered outcome pathways (AOPs), as well the development of prediction models for drug-induced toxicity.

Dr. José V. Castell
Dr. Marta Moreno-Torres
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Metabolites is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

• metabolomics
• toxicometabolomics
• lipidomics
• preclinical toxicology
• preclinical drug safety
• drug discovery
• biomarker discovery
• liver, kidney
• cardiac
• neural
• hematopoietic metabolomics