Disposable in-tip cellulose paper device functionalized with clove essential oil for green and efficient extraction of abusable prescription drugs

A novel, green, and cost-effective microextraction method based on a disposable-in-tip cellulose paper (DICP) device was developed for the determination of three commonly abused prescription drugs; dextromethorphan (DXM), tramadol (TRM), and clozapine (CLZ); in human urine samples. The DICP device was fabricated by dip-coating cellulose paper with 1 % clove essential oil (CEO), which imparts amphiphilic properties to the cellulose surface, enhancing its sorptive interaction with analytes of moderate polarity. The extraction was carried out using 50 manual aspiration–dispensing cycles, followed by 40 aspiration–dispensing cycles for desorption of target analytes with 500 µL of methanol. The proposed method is extremely cost-effective and high-throughput, enabling the preparation of 12 samples per hour, with 30 extraction strips obtained from a single cellulose disc. The mechanism of extraction relies on the synergistic interaction between cellulose hydroxyl groups and the eugenol-rich CEO layer, facilitating the adsorption of analytes through combined hydrophilic and hydrophobic interactions. The method demonstrated excellent analytical performance, with limit of quantifications (LOQs) between 0.06–0.09 µg mL^-1, linearity (R² > 0.994), intra-day and inter-day precision below 7 % and 13 %, respectively, and accuracy ranging from 86 to 110 %. Blind urine sample analysis confirmed the method’s reliability for real-world application. Furthermore, the protocol achieved a click analytical chemistry index (CACI) score of 85 and a ComplexMoGAPI score of 83, highlighting its outstanding greenness, simplicity, and field-deployability for forensic and toxicological applications.