Liquid-filled stick microextraction with a built-in acidifier enabling pH-adjustment-free analysis of illegal NSAIDs...

This study presents a liquid-filled stick microextraction method with a built-in acidifier (LFSME-BA) that enables ready-to-use, pH-adjustment-free extraction of non-steroidal anti-inflammatory drugs (NSAIDs) from complex herbal matrices. Similar to an alcohol swab, the device contains an H₃PO₄-saturated hydrophobic deep eutectic solvent (DES) loaded inside a hollow plastic stick and a polypropylene fabric tip. Upon use, the acidified DES is released and absorbed by the fabric tip. When immersed in the sample solution, H₃PO₄ gradually diffuses outward and, in the aqueous model solution used in this study, reduces the sample pH to approximately 1.97. This in situ acidification converts the NSAIDs from their ionized forms to their neutral molecular species, markedly increasing hydrophobicity, thereby facilitating their diffusion into the DES phase. Following desorption with 0.4 mL acetonitrile and LC-UV analysis, the LFSME-BA method provided excellent linearity (R² ≥ 0.994, 20-2000 ng/mL), low detection limits (3.04-5.80 ng/mL), and satisfactory accuracy (93.7-102.5%) and precision (RSD ≤ 8.3%). Application to herbal oral liquids and granules yielded relative recoveries of 85.1%-108.8%, further confirming the method's reliability. This ready-to-use, disposable platform combines extraction and pH self-regulation in one step, offering a simple and efficient approach for screening adulterated pharmaceuticals in herbal products.