Thermal (In)stability of Atropine and Scopolamine in the GC-MS Inlet

The intoxication due to unintentional or intentional ingestion of plant material containing tropane alkaloids is quite frequent. GC-MS method is still widely used for the identification of these toxicologically important substances in human specimen. During general unknown analysis, high temperature of inlet, at least 270 °C, is commonly used for less volatile substances. Unfortunately, both tropanes are thermally unstable and could be overlooked due to their degradation. The temperature-related degradation of tropanes atropine and scopolamine was systematically studied in the inlet of a GC-MS instrument in the range 110–250 °C by increments of 20 °C, additionally also at 275 °C, and in different solvents. At inlet temperatures not higher than 250 °C, the degradation products were formed by elimination of water and cleavage of atropine’s ester bond. At higher temperatures, elimination of formaldehyde became predominant. These phenomena were less pronounced when ethyl acetate was used instead of methanol, while n-hexane proved unsuitable for several reasons. At an inlet temperature of 275 °C, tropanes were barely detectable. During systematic toxicological analysis, any tropanes’ degradation products should indicate the possible presence of atropine and/or scopolamine in the sample. It is not necessary to prepare thermally stable derivatives for confirmation. Instead, the inlet temperature can be decreased to 250 °C, which diminishes their degradation to a level where their detection and identification are possible. This was demonstrated in several case studies.

Systematic toxicological analysis using liquid chromatography-mass spectrometry: techniques and inter-instrument reproducibility of mass spectra/Systematisch-toxikologische Analyse mittels Hochleistungsflüssigchromatographie-Massenspektrometrie: Techniken und Reproduzierbarkeit von Massenspektren zwischen Instrumenten

The so-called systematic toxicological analysis (STA) aiming at simultaneous analysis of as many toxicologically relevant compounds in biosamples as possible is an important part of routine analysis in clinical and forensic toxicology. Gas chromatography-mass spectrometry and liquid chromatography with diode array detection have been the most widely used techniques for this purpose. However, in recent years STA methods based on liquid chromatography coupled to mass spectrometry (LC-MS) or tandem mass spectrometry (LC-MS/MS) have become increasingly important, although their widespread use is still hampered by the lack of a universal reference library of mass spectra that can be used on all major instrument platforms. In this review, LC-MS(/MS) methods for STA in urine and/or blood published in the past 6 years will be compared and discussed with regard to sample preparation, separation, instrument types used for mass spectrometric detection, and method validation. In addition, different approaches to achieving the goal of a universal reference library will be summarized.