From conventional to miniaturized workflows: a critical review of sample preparation methods for nonsteroidal anti-inflammatory drug analysis.

Non-steroidal anti-inflammatory drugs (NSAIDs) are extensively used pharmaceuticals that persist in biological fluids, environmental waters, and food, raising concerns for therapeutic monitoring, drug quality control, and ecological safety. Because trace-level detection is strongly dictated by pretreatment, recent research has shifted from conventional liquid-liquid extraction and solid-phase extraction toward miniaturized, greener, and automation-ready formats. Liquid-phase microextraction variants (e.g., DLLME, HF-LPME, EME, SALLE) and solid-phase microextraction methods (SPME, MEPS, DSPE, MSPE, QuEChERS) have demonstrated reduced solvent consumption, improved enrichment, and greater compatibility with complex matrices. Advanced sorbent materials, nanostructures, and hybrid designs offer enhanced selectivity but often face challenges of scalability, cost, and genuine sustainability. This review critically evaluates these approaches in terms of principles, performance, and limitations, highlighting trends in miniaturization, automation, and appliable metrics. The aim is to provide analytical scientists with a balanced perspective to guide matrix- and purpose-driven selection of NSAID extraction methods and to outline future directions toward standardized, high-throughput, and environmentally sustainable workflows.