Development and validation of analytical methods for drug monitoring and metabolomics

Metabolomics

Metabolomics is an integral part of the broader field of systems biology and has attracted increasing interest for studies in important life science disciplines such as pharmacy, toxicology and medicine. The metabolome is the set of all endo- and exogenous small molecular mass organic compounds (Mr < 1500) found in a given biological media. As metabolites are the ultimate downstream products of genomic, transcriptomic, and/or proteomic perturbations, changes in metabolite concentration and/or flux can reveal biologically relevant changes to the system. Thus, the primary task of metabolomics is the identification of markers or signatures that are characteristic for a defined biological system.We are using GC/MS and LC/MS as analytical techniques for qualitative and quantitative metabolome analysis. We are involved in several scientific projects. Several assays are available for immediate application. For other targets an assay development service is provided. Please contact Herbert Oberacher for more information.

Systematic toxicological analysis

Systematic toxicological analysis (STA) is a major part of the examination in forensic and clinical toxicology. STA is aimed at detecting and identifying all substances of toxicological relevance in biological material. Since the outcome of STA can have substantial legal and/or social consequences, several analytical procedures are run in sequence or in parallel to minimize the probability of a false positive or a false negative result.

Primary screening is usually accomplished with immunoassays. This kind of technology focuses on the analysis of a single drug or a certain family of drugs in each test. More universal screening tools are based on chromatographic methods hyphenated to appropriate spectroscopic/spectrometric methods. Gas chromatography mass spectrometry (GC/MS) is routinely applied. To complement the existing set of methods for STA, we propose the use liquid chromatography mass spectrometry (LC/MS) that allows identification of compounds via search within a tandem mass spectrometric library (i.e. Wiley Registry of Tandem Mass Spectral Data, MS for ID).

Therapeutic drug monitoring

Therapeutic drug monitoring (TDM) subsumes the surveillance of medically prescribed drugs in patients. Toxicological analytical methods play a major role in TDM, as the determination of the substances as well as their quantification in biological samples allow conclusions concerning compliance or metabolism characteristics and, therefore, effectiveness of the given drug. Especially for substances that show a small therapeutic range or for newly launched drugs TDM is essential for a safe clinical appliance. The analysis of drug concentrations in different tissues helps to find optimal application routes and to minimize unwelcome side effects.

With our TDM lab we are involved in several scientific projects. To provide reliable quantitative data, validated assays employing state-of-the-art GC/MS or LC/MS technology are used. A number of assays are available for immediate application. For other targets an assay development service is provided. Please contact Herbert Oberacher for more information.

Grant

Österreichische Forschungsförderungsgesellschaft: dnatox – Die Kopplung der Flüssigkeitschromatographie mit der Massenspektrometrie als Werkzeug für die Toxin- und DNA-Analytik, KIRAS PL 2 Projekt 813786, 2008-2009.

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