A validated screening and confirmation method for 946 drugs and metabolites using LC-QTOF-MS with SWATH acquisition

Area of Science:

• Forensic Toxicology
• Analytical Chemistry
• Mass Spectrometry

Background:

• Current toxicological screening methods may lack comprehensiveness for diverse drug classes.
• The need for rapid, accurate, and reliable methods for postmortem, DFC, and UID analyses is critical.

Purpose of the Study:

• To develop and validate a streamlined LC-QTOF-MS method for broad drug and metabolite screening.
• To enhance spectral clarity and analytical sensitivity for complex biological matrices.

Main Methods:

• Utilized liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS).
• Employed protein precipitation and filtration extraction with sequential window acquisition of all theoretical mass spectra (SWATH) acquisition.
• Validated the method per established guidelines, achieving limits of detection as low as 0.1 ng/mL.

Main Results:

• Successfully screened and confirmed 946 drugs and metabolites across 35 drug classes.
• Demonstrated high accuracy and reliability in 67 proficiency test and 224 authentic case samples.
• Accurate detection of traditional drugs and novel psychoactive substances (NPS) was achieved.

Conclusions:

• The developed LC-QTOF-MS method provides rapid, reliable, and comprehensive toxicological analysis.
• This method meets and exceeds requirements for postmortem, DFC, and UID testing.
• Enhanced analytical capabilities improve detection rates and streamline forensic investigations.