Universal LC–MS/MS Screening for GHB: Advancing Routine Detection in Postmortem Toxicology and Accuracy of Death Investigations

Gamma-hydroxybutyric acid (GHB) is an endogenous compound and central nervous system depressant with legitimate therapeutic applications but frequent illicit use. Historically, GHB has been excluded from routine systematic toxicology testing because its detection typically required targeted analysis, limiting testing to cases where GHB use was specifically suspected. In 2020, our office implemented a validated LC-MS/MS screening platform that enabled GHB to be analyzed efficiently and universally across all forensic case types, including postmortem death investigations. Between May 2020 and April 2025, 15 GHB-associated fatalities were identified, with 11 (73%) having no investigative suspicion of GHB use. Most decedents were male, White, with the cohort having a median age of 39 years. Twelve deaths (80%) were accidental, and three (20%) were suicides. Concentrations in both blood and urine were consistent with exogenous exposure across all cases, frequently in the context of polysubstance stimulant use. Integration of GHB testing into routine testing workflows revealed multiple previously unrecognized fatalities, demonstrating that universal inclusion of GHB enhances accuracy in death certification, operational efficiency, and the completeness of forensic toxicology surveillance.