Modern drug testing in clinical laboratories: a narrative review of practical approaches and emerging technologies

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Background and Objective: Clinical toxicology testing plays a critical role in patient care by supporting drug management, detecting toxic exposures, and monitoring medication adherence. With the increasing complexity of drug use patterns and the need for rapid, accurate diagnostics, toxicology laboratories must strategically select specimen types and analytical platforms that align with clinical needs. This review aims to summarize key aspects of toxicology testing, including specimen selection, screening and confirmation technologies, and result interpretation. It also highlights emerging trends and innovations that may shape the future of clinical toxicology. Methods: A narrative review of current toxicology practices was conducted, focusing on the clinical utility and limitations of common matrices (urine, blood, oral fluid, hair, neonatal specimens, breath, and fingerprint sweat), screening technologies (immunoassays, point-of-care tests, mass spectrometry), and confirmatory techniques (gas chromatography, liquid chromatography, and mass spectrometry). Databases and other sources searched included PubMed, textbooks, scientific organizations, vendor websites, College of American Pathologists (CAP) resources, and Clinical & Laboratory Standards Institute (CLSI) guidance documents. These were referenced between January and September 2025, and only those written in English were considered. Literature and guideline references were integrated with practical insights for laboratory implementation. Key Content and Findings: Each specimen matrix offers unique advantages and limitations regarding detection window, invasiveness, and interpretability. While urine remains the dominant matrix for drug screening, oral fluid and other emerging specimens (e.g., breath, fingerprint sweat) offer new opportunities for noninvasive testing. Immunoassay-based screens, while rapid and widely used, are vulnerable to false-positive and -negative results. Mass spectrometry-based methods provide superior specificity and breadth but require greater technical expertise and infrastructure. Technological advances—including automated mass spectrometry platforms and artificial intelligence (AI)-assisted interpretation—aim to address barriers to implementation and improve turnaround time, standardization, and clinical utility. Result interpretation remains a major challenge due to complex pharmacokinetics and limited clinician training; input from an expert toxicologist is essential to avoid misinterpretation and ensure appropriate follow-up. Conclusions: Optimizing toxicology testing requires a balance between analytical performance, clinical context, and operational feasibility. Continued advancements in analytical technologies, specimen diversity, and data interpretation tools hold promise for enhancing diagnostic accuracy and clinical decision-making in toxicology. Expert oversight and appropriate test utilization will remain pivotal in maximizing the impact of laboratory toxicology services.

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