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

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.