For the first time, a novel biofluid sampler (BFS) and sample preparation device is applied for the analysis of 11 basic drugs (i.e., pheniramine, chlorpheniramine, fluoxetine, tramadol, amitriptyline, ketamine, diazepam, chlordiazepoxide, clozapine, chlorpromazine, dothiepin) in biological matrices (i.e., blood and urine). BFS utilizes advanced, highly effective sorbents derived from sol-gel sorbent coating technology onto cellulose fabric substrate, improving sample collection and retention. BFS has the capability to retain a biological sample from 10 to 1000 µL without requiring any dilution or pre-treatment of the sample. The biological samples were pipetted onto the BFS device and dried at room temperature. Subsequently, adsorbed analytes were back-extracted into 1000 µL of methanol without requiring any imposed external diffusion process and then analyzed by gas chromatography-mass spectrometry (GC-MS). A one-factor-at-a-time (OFAT) screening procedure was used to extensively screen and optimize several parameters, including sample volume, elution time, solvent volume, and solvent type. Under the optimal conditions of the study, the method was found to be linear within the range 0.1–10 µg mL−1 for both blood and urine. Quantification limits were established for blood samples within the range of 0.072–0.095 μg mL−1 and for urine samples within the range of 0.050–0.069 μg mL−1. The precisions within and between days were less than 7% and 10%, respectively. The target analytes showed good recoveries utilizing the recommended protocol, with ranges of 45.1%–103.4%. Furthermore, the methodology has been effectively implemented in forensic toxicology case work. Moreover, the green characteristics and applicability of the suggested methodology was evaluated using softwares i.e., AGREE and BAGI.
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