Methamphetamine and its isotopologues - a case study on the potential challenges encountered in the detection and quantification of isotopically labelled drugs of abuse.

Isotopically labelled compounds, particularly isotopologues, are commonly used in analytical laboratories as internal standards for mass spectrometry-based quantitative analysis. Their comparable behavior during LC-MS/MS analysis makes them reliable tools for accurate detection and quantification. In addition to their analytical applications, some isotopically labelled compounds are also used as pharmaceuticals. This raises the possibility that such compounds may also be encountered as drugs of abuse, highlighting the need for their consideration in forensic and toxicological analysis. In the present preliminary study, we show the challenges that deuterated (in general, isotopically labelled) drugs of abuse pose in clinical toxicology, doping control and forensic laboratories. On the examples of deuterated isotopologues of methamphetamine we demonstrate that it is not possible to detect isotopologue drugs of abuse based on the current standard methodologies used by clinical toxicology and forensic laboratories. We also discuss a possible (partial) solution around this problem.