Overview of systematic toxicological analysis strategies and their coverage of substances in forensic toxicology

Abstract

Systematic toxicological analysis (STA) is the process of using an adequate analytical methodology to detect and identify as many potentially toxicologically relevant compounds as possible in biological samples. STA is an important part of everyday routine work within forensic toxicology, and several methods for STA have frequently been published and reviewed independently. However, the many drugs and other substances involved, as well as the constant emergence of new ones, may pose a major challenge in STA, which often demands a strategy involving multiple analytical methods in parallel. Such strategies have been published and evaluated less frequently despite their relevance in forensic toxicology. This mini-review briefly summarizes commonly applied methods for STA in forensic toxicology, including gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-MS (LC-MS) methods, and highlights some of their potential pitfalls. Second, it provides an overview of previously reported strategies to conduct STA, including a presentation of the STA strategy applied in the authors' laboratory. This involves broad drug screening by LC-high-resolution MS, supported by targeted screening and quantification using LC-tandem MS, headspace (HS)-GC-MS, HS-GC-flame ionization detector and other complementary methods. The STA strategy aims to cover as many potentially relevant drugs as possible and seeks to reduce potential pitfalls arising in forensic casework. The review underlines that not every substance can be identified in all circumstances even with a comprehensive STA strategy.

Keywords: STA; drug screening; forensic toxicology; high‐resolution; mass spectrometry.

FIGURE 1

Overview of the STA strategy and method setups applied for postmortem cases in the authors’ laboratory. Screening and simultaneous targeted screening and quantification are initially performed, indicated by (1), and quantification of positive screening results is then performed, indicated by (2). The methods are indicated by I–XI. Method VI is performed in vitreous humour/urine. For further explanations see section 4.1. Abbreviations: BHB: beta‐hydroxybutyric acid, DOA: drugs of abuse, GC: Gas chromatography, GHB: gamma‐hydroxybutyric acid, HbA1c: hemoglobin A1c, LC: liquid chromatography, MS: mass spectrometry, NPSs: New psychoactive substances, PPT: protein precipitation, SPE: solid phase extraction, TOF: Time of flight.