Systematic Toxicological Analysis

Systematic Toxicological Analysis

Development and application of non-targeted LC-MS/MS for 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.

Primarily 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. We propose the use of non-targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS), which allows identification of compounds via search within a tandem mass spectrometric library (i.e. Wiley Registry of Tandem Mass Spectral Data, MSforID.

We have successfully developed and applied non-targeted LC-MS/MS for forensic-toxicological analysis of various human specimens, including blood, plasma/serum, urine, and saliva.


The principles of LC-MS-based STA have been summarized in the following review articles:

  1. Oberacher, H., Arnhard, K.
    Current Status of Non-targeted Liquid Chromatography-Tandem Mass Spectrometry in Forensic Toxicology
    Trends in Analytical Chemistry, 84 (2016), 94-105.
  2. Oberacher, H., Arnhard, K.
    Compound Identification in Forensic Toxicological Analysis with Untargeted LC/MS-based Techniques
    Bioanalysis, 7 (2015), 2825-2840.


Different aspects of the analytical process were discussed in the following publications:

  1. Stempfer, M., Reinstadler, V., Lang, A., Oberacher, H. Analysis of Cannabis Seizures by Non-targeted Liquid Chromatography-Tandem Mass Spectrometry Journal of Pharmaceutical and Biomedical Analysis, 205 (2021) 114313.
  2. Hornek-Gausterer, R., Oberacher, H., Reinstadler, V., Hartmann, C., Liebmann, B., Lomako, I., Scharf, S., Posautz, A., Kübber-Heiss, A.* Detection of Potential Environmental Contaminants in the European Brown Hare (Lepus Europaeus) by Suspect and Microplastics Screening Environmental Advances, 4 (2021), 100045.
  3. Oberacher, H., Sasse, M., Antignac, J.-P., Guitton, Y., Debrauwer, L., Jamin, E. L., Schulze, T., Krauss, M., Covaci, A., Caballero-Casero, N., Rousseau, K., Damont, A., Fenaille, F., Lamoree, M., Schymanski, E. L.* A European Proposal for Quality Control and Quality Assurance of Tandem Mass Spectral Libraries Environmental Science Europe, 32 (2020), 43.
  4. Oberacher, H., Reinstadler, V., Kreidl, M., Stravs, M. A., Hollender, J., Schymanski, E. L.* Annotating Non-targeted LC-HRMS/MS Data with Two Complementary Tandem Mass Spectral Libraries Metabolites, 9 (2019), 3.
  5. Reinstadler, V., Lierheimer, S., Boettcher, M., Oberacher, H.
    A Validated Workflow for Drug Detection in Oral Fluid by Non-targeted Liquid Chromatography-Tandem Mass Spectrometry
    Analytical and Bioanalytical Chemistry, 411 (2019), 867-876.
  6. Pitterl, F., Köb, S., Pitterle, J., Steger, J., Oberacher, H. Applying Low-Resolution Tandem Mass Spectrometry with Subsequent Library Search for Reliable Compound Identification in Systematic Toxicological Analysis LCGC, 29 (2016), 419-427.
  7. Arnhard, K., Gottschall, A., Pitterl, F., Oberacher, H. Applying ‘Sequential Windowed Acquisition of All Theoretical Fragment Ion Mass Spectra’ (SWATH) for Systematic Toxicological Analysis with Liquid Chromatography – High-Resolution Tandem Mass Spectrometry
    Analytical and Bioanalytical Chemistry, 407 (2015), 405-414.
  8. Oberacher, H., Schubert, B., Libiseller, K., Schweissgut A
    Detection and Identification of Drugs and Toxicants in Human Body Fluids by Liquid Chromatography-Tandem Mass Spectrometry under Data-dependent Acquisition Control and Automated Database Search
    Analytica Chimica Acta, 770 (2013), 121-131.
  9. Schubert, B., Oberacher, H. Impact of Solvent Conditions on Separation and Detection of Basic Drugs by Micro Liquid Chromatography-Mass Spectrometry under Overloading Conditions
    Journal of Chromatography A, 1218 (2011), 3413-3422.