Miniaturized design for the extraction of antidepressants from postmortem blood using disposable in-tip cellulose paper device: A sustainable and low carbon foot print approach.

Antidepressant drugs are frequently encountered in forensic toxicology due to their extensive use and involvement in overdose and fatal poisoning cases, making their determination in postmortem blood analytically and clinically significant. In this study, a sustainable and miniaturized extraction approach based on a clove essential oil-impregnated disposable in-tip cellulose paper device was developed for the green extraction and determination of antidepressants from postmortem blood by gas chromatography-mass spectrometry. In the proposed device, cellulose paper, a renewable and biodegradable biopolymer, was impregnated with clove essential oil rich in eugenol, which plausibly forms hydrogen bonds with cellulose hydroxyl groups, producing a dual-polarity sorbent surface capable of hydrogen bonding, π-π stacking and hydrophobic interactions with antidepressant molecules. This modification enhanced extraction efficiency without the need for synthetic sorbents or energy-intensive preparation. The optimized procedure involved 0.5 mL of blood diluted to 5 mL (pH 11), followed by 60 aspirating/dispensing cycles for adsorption and 40 cycles for desorption using 0.5 mL of ethanol. The method exhibited excellent linearity (R2 = 0.990-0.997), limit of quantifications of 0.072-0.95 μg mL-1, accuracy of 89.1-104.4%, and precision within 3.4-12.5%, with recoveries between 75.4 and 92.2% and negligible matrix effects (<8.7%). Greenness and sustainability assessments using Carbon Footprint Reduction Index, Analytical Green Star Area, and Blue Applicability Grade Index tools confirmed a low carbon footprint, minimal environmental impact, and strong alignment with the principles of White Analytical Chemistry. Application to real postmortem blood samples demonstrated successful detection of antidepressant drugs, validating the method's forensic applicability. Overall, the developed method provides a simple, affordable, and eco-friendly alternative for antidepressant analysis, offering rapid extraction, minimal solvent use, and low environmental burden, making it a practical and sustainable solution for routine forensic toxicology.