Targeted Comprehensive Screening of Neuropsychiatric Drugs in Serum by LC-MS/MS: Method Development and Three-Year...

Area of Science:

• Clinical Chemistry
• Pharmacology
• Analytical Chemistry

Background:

• Growing misuse of neuropsychiatric medications necessitates efficient clinical laboratory drug screening.
• Serum analysis is vital for detecting current drug exposure, intoxication causes, and medication adherence.
• Current broad serum drug screening applications using liquid chromatography-tandem mass spectrometry (LC-MS/MS) are limited in clinical settings.

Purpose of the Study:

• To develop and validate an LC-MS/MS method for simultaneous qualitative identification of 77 neuropsychiatric drugs.
• To assess the method's large-scale clinical application over three years.
• Utilizing multiple reaction monitoring and information-dependent acquisition-triggered enhanced product ion scans for comprehensive drug detection.

Main Methods:

• Method validation encompassed precision, accuracy, recovery, matrix effects, selectivity, and interference.
• A minimal serum volume (20 μL) required simple protein precipitation with <15 minutes preparation time per batch.
• The method was applied to 1,021 clinical serum specimens, with chromatographic separation in 15 minutes.

Main Results:

• High accuracy (100% agreement for 60 analytes) and recovery (93.1%) were achieved.
• Benzodiazepines (37.9%), antidepressants (30.7%), and antipsychotics (19.7%) were the most frequently detected drug classes.
• Emergency Medicine patients showed a higher positivity rate, with clonazepam/7-aminoclonazepam (10.2%) and lorazepam (10.0%) being common analytes.

Conclusions:

• A validated LC-MS/MS method allows simultaneous detection of numerous neuropsychiatric drugs in serum.
• The method is essential for verifying medication history, identifying non-adherence, and diagnosing acute intoxication.
• Broad-spectrum serum screening plays a critical role in managing medication-related emergencies and optimizing patient care.