Detection of ∆9-THC in cerebrospinal fluid: new validation strategies for forensic and clinical toxicology applications

Cannabis remains one of the most abused substances, necessitating accurate toxicokinetic profiling of cannabinoids in biological matrices. Cerebrospinal fluid (CSF) offers advantages like lower contamination and minimal post-mortem redistribution, and can enable detection of CNS-acting substances like ∆9-THC linked to neuropsychiatric disorders. However, the validation of analytical methods in CSF has been challenging due to the limited availability of authentic samples. This study aims to overcome this limitation by developing and fully validating a sensitive and specific LC-MS/MS method for the detection of ∆9-THC using an artificial CSF matrix. Validation studies were performed for selectivity, LOD, LOQ, linearity, precision, accuracy, and stability. The calibration curve ranged from 0.5 to 50 ng/mL. LOD and LOQ values were determined to be 0.4 and 0.5 ng/mL, respectively. The mean recovery and RSD values were 81.38 and 4.41, respectively. The validated method was applied to a CSF sample from a patient with a history of cannabis use. This approach not only facilitates method development and validation in situations where actual CSF samples are scarce but also offers a new perspective for cannabinoid monitoring by expanding the application of CSF as an alternative to traditional biological samples in forensic and clinical toxicology.