False positive urine drug screens

Immunoassay-based urine drug screens are widely employed in clinical toxicology due to their speed, low cost, and ease of automation. However, these assays are inherently limited by antibody cross-reactivity, which can result in false-positive findings and incorrect interpretations with major implications for patient care, employment, and legal outcomes. This review updates prior literature by analyzing reported false-positive interferences published between 2013 and 2024 across commonly screened drug classes, including opioids, amphetamines, benzodiazepines, cannabinoids, barbiturates, phencyclidine (PCP), cocaine, ethanol, and ethyl glucuronide. A total of 61 studies met inclusion criteria from 569 unique publications retrieved via PubMed. Each report was categorized by level of evidence, ranging from single case reports to controlled spiking experiments. Despite advances in antibody specificity, immunoassay drug screens remain presumptive and require confirmation by orthogonal techniques such as gas or liquid chromatography coupled with mass spectrometry (GC-MS or LC-MS/MS). This review provides updated reference data on known interferents, emphasizes the need for laboratorian-clinician communication, and supports continued education on assay limitations. Reliable interpretation of presumptive immunoassay drug screen results remains essential to prevent inappropriate clinical care decisions.