Development and Implementation of One-Step, Broad-Spectrum, High-Sensitivity Drug Screening by Tandem Mass...

Area of Science:

• Clinical Chemistry
• Forensic Toxicology
• Pediatric Drug Monitoring

Background:

• Immunoassay drug screening is prevalent in pediatric settings.
• Common issues include false positives/negatives due to antibody cross-reactivity and dilute urine.
• Accurate drug exposure data is critical for pediatric clinical and medico-legal contexts.

Purpose of the Study:

• To develop and validate a liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for pediatric urine drug screening.
• To compare the performance of LC-MS/MS with traditional immunoassay methods.
• To analyze the frequency and types of drug detection in a pediatric population post-implementation.

Main Methods:

• Development and characterization of a broadly targeted LC-MS/MS assay for 38 compounds.
• Retrospective analysis of 3985 pediatric urine drug screens (1663 pre-implementation, 2322 post-implementation).
• Comparison of immunoassay results with LC-MS/MS confirmation and post-implementation LC-MS/MS data.

Main Results:

• Immunoassays showed high rates of presumptive positives (23% general pediatric, 37% nursery), with significant discrepancies upon mass spectrometry confirmation (85% general pediatric, 40% nursery confirmed).
• Post-LC-MS/MS implementation, 31% of general pediatric and 18% of nursery samples tested positive.
• LC-MS/MS identified a broader range of compounds, notably under-detecting THC and over-detecting cocaine with immunoassays in the nursery population.

Conclusions:

• A broadly targeted, sensitive LC-MS/MS assay offers superior detection of multiple drug compounds in a single step compared to immunoassay screen-then-confirm.
• Accurate and rapid results from LC-MS/MS facilitate timely patient management in diverse clinical settings.
• LC-MS/MS provides a more comprehensive and accurate assessment of pediatric drug exposure.