Comparative evaluation of tandem dispersive and modified hollow fiber liquid-phase microextraction techniques for sensitive determination of NSAIDs in complex biological matrices

• Providing guidance for sensitive NSAIDs determination in complex biological matrices. • Comparative study of TDLLME and modified HF-LPME for NSAID analysis. • Optimized extraction of diclofenac, ibuprofen, and mefenamic acid. • Both methods validated in urine, saliva, hair, and nail samples. • Modified HF-LPME showed higher enrichment and lower detection limits. • TDLLME offered faster extraction with simpler equipment needs. Two advanced microextraction techniques possessing greater cleanup capacity— TDLLME (Tandem Dispersive Liquid-Liquid Microextraction) and modified HF-LPME (Hollow Fiber Liquid Phase Microextraction)—were comparatively evaluated here for selective preconcentration and determination of NSAIDs (nonsteroidal anti-inflammatory drugs), i.e., diclofenac, ibuprofen, and mefenamic acid, from complex biological samples. Both the methods were coupled with HPLC-UV (high-performance liquid chromatography-ultraviolet detection) for sensitive detection. Key parameters like the nature and amount of organic solvents, pHs in acceptor and donor phases, ionic strength, number of extraction cycles, agitation (stirring) rates, and time of extraction were optimized using a one-variable-at-a-time pathway. Results revealed that modified HF-LPME method, with 1-octanol in a three-phase system and magnetic stirring assistance, provided improved analytical performance through enrichment factors of up to 183.6, extraction recoveries greater than 77%, and extremely low detection limits of 0.1 ng mL −1 . In contrast, the TDLLME technique demonstrated the advantage of considerably shorter extraction time of only 25 minutes with less complex equipment, albeit with comparatively lower enrichment factors and sensitivity. Validation with real biological matrices—urine, saliva, hair, and nails—verified the reliability and accuracy of both methods, with relative recovery rates always in the range of approximately 94% to 102% and relative standard deviations of lesser than 5.3%. TDLLME can be a handy route for rapid screening, whereas the improved HF-LPME method is more appropriate if ultra-trace sensitivity is essential. These results provide valuable recommendations for sample preparation strategy choice balancing speed, sensitivity, and environmental factor considerations in pharmaceutical analysis.