An integrated white analytical platform based on rotating paper disc microextraction and in-injector micro-reaction for forensic determination of non-steroidal anti-inflammatory drugs in complex biological matrices.

This study presents, for the first time, an integrated analytical strategy combining a rotating paper disc (RPD) microextraction device with in-injector micro-reaction (IIMR) for the determination of seven non-steroidal anti-inflammatory drugs (NSAIDs) in postmortem biological matrices. The proposed approach employs a cellulose-based sorptive phase impregnated with octanol, enabling efficient and low-cost extraction through enhanced amphiphilic. The design of RPD device promotes efficient mass transfer and facilitates direct immersion into complex matrices such as liver, blood, and urine, allowing rapid and effective analyte uptake without the need for complex sorbent synthesis or extensive sample handling. The IIMR concept represents an on-line, instrument-mediated and non-discrete transformation that occurs directly within the GC injection port during sample introduction, thereby eliminating any additional derivatization step. This embedded micro-reaction proceeds instantaneously under injector conditions (within seconds), requires no external heating or reaction time, and consumes ultra-low volumes of reagent (1 μL), significantly improving analytical throughput and reducing chemical usage compared to conventional derivatization protocols. Under optimized conditions, the method exhibited satisfactory linearity (0.1-10 μg mL-1 or μg g-1), good accuracy (86.8-101.1%), low limits of quantification (0.033-0.099 μg mL-1 or μg g-1), and excellent precision (1.8-10.7%). The overall analytical workflow demonstrated strong alignment with green and white analytical chemistry principles, as confirmed by AGSA (70.83) and BAGI (70) scores. The method was successfully applied to real postmortem liver, urine, and blood samples, highlighting its robustness, operational simplicity, and suitability for routine forensic toxicology applications.