Ropinirole metabolite mimics a new psychoactive substance (4-HO-MET) in LC-MS/MS

A metabolite of the medication ropinirole (N-despropyl-ropinirole) can cause a false positive for the new psychoactive substance 4-HO-MET in urine drug screening by liquid chromatography tandem mass spectrometry (LC-MS/MS), a method usually considered highly reliable. The interference occurred because the two compounds share similar chemical structures, which fooled standard computer-aided spectral library matching. Careful manual review of mass spectra and comparison with a reference specimen correctly identified the compound. The finding underscores that scientists and pathologists must consider clinical context and drug history when interpreting toxicology results, and that mass spectra should be checked for relative ion ratios when results are questionable. Understanding drug metabolism is essential for troubleshooting such errors.

Study at a glance

Abstract

Liquid chromatography tandem mass spectrometry (LC-MS/MS) is often regarded as a highly reliable methodology for confirmatory testing in analytical toxicology, especially for detection of new psychoactive substances (NPS) by clinical and forensic laboratories. However, false positives still do occur and erroneous reporting can have substantial legal implications. In this study, we investigated into the mechanism behind a clinically implausible, but apparently analytically sound, finding of a NPS (4-hydroxy-N-methyl-N-ethyltryptamine; 4-HO-MET) in a urine specimen for toxicology screening by LC-MS/MS. We discovered that a ropinirole metabolite (N-despropyl-ropinirole) was the culprit of interference as it shares high structural similarities with 4-HO-MET. The chemical similarities eluded various rigorous regulatory guidelines for compound identification utilizing computer-aided spectral library matching. After careful scrutiny of the mass spectra and comparison with a reference specimen, the compound was correctly identified. Our findings emphasize the important synergy between scientists and pathologists in considering the clinical context, especially drug history, in clinical and forensic toxicology analysis on biological specimens. Mass spectra should be reviewed for relative ion ratios in case of doubt. Understanding drug metabolism is essential for troubleshooting and result interpretation.