Determination of ten antipsychotics in blood, hair and nails: Validation of a LC-MS/MS method and forensic application of keratinized matrix analysis

Determination of antipsychotics from biological samples is meaningful in the field of clinical and forensic medicine. Compared to blood, keratinized matrices such as hair and nails have attracted increasing attention in drug analysis for wider detection window. Nevertheless, the distribution and stability of antipsychotics in keratinized matrices are not clarified yet. Therefore, we developed a LC-MS/MS based method for simultaneous determination of 10 antipsychotics from blood, hair and nails, with high recovery (78.1-107.4%, 71.3-93.5% and 75.2-90.5%), low LOD (5-10 pg/mL, 5-10 pg/mg and 5 pg/mg) and high accuracy (96.0%-101.6%, 97.5%-102.5% and 97.6-101.7%). The method was applied to sets of blood, hair, and nail samples of 54 patients who received long-term therapy, and significant correlations between drug concentrations in blood and hair was found, while the correlation between nails and other matrices varied depending on the drug. Except for olanzapine, the concentrations of antipsychotics in segmental hair samples were consistent with drug exposure. Besides, the hair and nail samples of suspects in two forensic cases were analyzed and provided supporting evidence for the suspects' psychiatric state. Our research offered a deeper understanding of keratinized matrix as stable and retrospective bio-samples for antipsychotics detection in forensic practice.