Evaluation of a Targeted LC–MS/MS Assay for Clinical Quantification of Urinary Organic Acids

ABSTRACT

Gas chromatography–mass spectrometry (GC–MS) is the reference method for urine organic acid analysis but requires complex sample preparation and derivatization, limiting routine clinical use. We developed and validated a targeted Liquid chromatography–tandem mass spectrometry (LC–MS/MS) method for quantifying urinary organic acids relevant to the evaluation of inborn errors of metabolism. The assay demonstrated excellent linearity, precision, accuracy, analytical sensitivity, and good agreement with GC–MS. Organic acidurias and other metabolic disorders were accurately identified through characteristic metabolite elevations. The simplified workflow eliminates derivatization and enables rapid, high‐throughput implementation for newborn screening confirmation, metabolic screening, and patient monitoring in pediatric clinical laboratories.