The consumption of alcohol and other substances of abuse poses significant risks, including dependency, health complications, and amplified dangers from polysubstance use. In this study, a multi-analyte LC–MS/MS method was developed for the determination of cocaine and its alcohol-derived metabolite, cocaethylene, as well as three PEth homologues and eleven other drugs and metabolites,including opioids, local anesthetics, and hallucinogens, in whole blood.

Sample preparation was performed through liquid–liquid extraction. Chromatographic separation was achieved on a C18 column, with a mobile phase of 0.025% ammonia, pH = 10.7, and methanol.

The method was fully validated. The inter-assay precision and accuracy were < ± 16% for all compounds at five of the seven concentrations. The recovery was within 42-79% for 15 compounds and 11% for benzoylecgonine. Matrix effects were minimal for eight compounds, while LSD and four of the five opioids presented ion enhancement, and the PEth homologues showed ion suppression. However, the internal standards compensated for these effects.

The validated method is precise, accurate, robust, and sensitive. It is designed for the determination of cocaine, cocaethylene, crack cocaine, PEth homologues, and 10 other drugs and their metabolites in whole blood. This makes it highly useful in forensic toxicology for drug identification, clinical monitoring to assess drug use, and legal or workplace drug testing.