From over-the-counter to criminal evidence: Pharmacological profiles, analytical methods, and forensic insights into diphenhydramine's role in drug-facilitated crime.

BACKGROUND: Diphenhydramine (DPH), a widely available over-the-counter antihistamine, has increasingly been implicated in DFCs, including sexual assault, pediatric abuse, and homicide. In several forensic investigations, DPH was detected in up to 13% of DFCs cases, with the highest prevalence reported in South Africa (12.1%), followed by France (10.0%) and the United States (10.2%). The sedative and amnestic effects of this drug, along with how easily it can be obtained, make it a substance of concern in DFCs. Detecting the drug can be challenging, mainly when metabolism occurs quickly, and there are delays in sample collection or case reporting.

METHODS: A systematic review was carried out across major scientific databases, such as PubMed, and Scopus, using relevant keywords. Additionally, reports from international bodies such as the United Nations Office on Drugs and Crime (UNODC) and the Society of Hair Testing (SoHT) were also reviewed.

RESULTS: The review compiles case evidence of DPH misuse, details its pharmacokinetics and toxicodynamics, and evaluates detection in biological matrices (blood, urine, hair, oral fluid). Analytical approaches, including LC-MS/MS, UHPLC-MS/MS, and LC-HRMS, are discussed, along with sample extraction methods including liquid-liquid and solid-liquid extraction.

CONCLUSIONS: DPH poses unique forensic challenges due to its low detectability and legal status. Hair analysis and high-resolution techniques offer extended detection capabilities in delayed cases. Increased forensic vigilance and validated analytical workflows are essential to address the covert misuse of DPH in DFCs.