Toxicological Evaluation of Emerging One-Step Urinary Multi-Drug Test Panels for Detecting Substance Abuse among Apparently Healthy Prospective Blood Donors: A Systematic Review

Background: Blood safety is threatened by prospective donors under the influence of psychoactive substances such as opioids, cannabinoids, and amphetamines. These substances can go undetected during routine donor screening, posing a risk to blood supplies worldwide. Urinary multi-drug test kits offer rapid screening, but their effectiveness and reliability require evaluation. Aim: To evaluate the toxicological performance and operational impact of urinary multi-drug screens for detecting substance use in blood donors. Methods: A literature review was conducted of studies evaluating urinary multi-drug test kits for detecting substance use among prospective blood donors. Searches included PubMed, Scopus, Google Scholar, and other databases. A total of 466 articles (77.7%) were retrieved out of 600 articles (100%) screened. The search terms used as in the text were: "urinary multi-drug test kits", "blood donor screening", "substance abuse detection", "psychoactive substances", "donor safety", and "toxicology testing". The systematic review triangulated manufacturer inserts, WHO/FDA guidance, and forensic toxicology literature (2020–2026). Results: Test panels showed high sensitivity (>90%) for classical drugs, but specificity was lower (75–88%) due to cross-reactivity and designer drug analogs. Fentanyl analogs and xylazine were frequently undetected. Cut-off values designed for workplace testing misclassified passive tetrahydrocannabinol(THC) exposure. Urine adulteration occurred in ∼5–12% of unsupervised collections. Confirmatory LC-MS/MS testing was required for positive screens, increasing operational costs by ∼2.5-fold. Main Findings: Emerging urinary multi-drug test kits require careful evaluation and validation before implementation. Unmodified workplace panels are unsuitable for donor screening without confirmatory testing and updated antibodies targeting newer substances. Conclusion: These kits can be a useful adjunct but have important limitations and biases. When embedded in ethical, consent-driven pathways, multi-drug panels may deter high-risk donations; otherwise, they risk undermining donor trust and analytical validity.