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Effervescent SiO2–drug–Na2CO3 composite nanoparticles were prepared in this study using a tetraethyl orthosilicate hydrolysis method to achieve a better release effect of hydrophobic drugs and spontaneous nanocarrier disintegration by dissolution.

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In this work, we developed and validated a highly sensitive, rapid and stable LC–MS/MS method for the determination of ibuprofen in human plasma with ibuprofen‐d3 as a stable isotopically labeled internal standard (SIL‐IS). Human plasma samples were prepared by one‐step protein precipitation. The chromatographic separation was achieved on a Poroshell 120 EC‐C18 (2.1 × 50 mm, 2.7 μm). Aqueous solution (containing 0.05% acetic acid and 5 mm NH4Ac) and methanol were selected as the mobile phase with gradient elution. An electrospray ionization source was applied and operated in negative ion mode. Multiple reaction monitoring mode was used for quantification using target fragment ions m/z 205.0 → 161.1 for ibuprofen and m/z 208.0 → 164.0 for SIL‐IS, respectively. This method exhibited a linear range of 0.05–36 μg/ml for ibuprofen with correlation coefficient >0.99. Mean recoveries of ibuprofen in human plasma ranged from 78.4 to 80.9%. The RSD of intra‐ and inter‐day precision were both < 5%. The accuracy was between 88.2 and 103.67%. The matrix effect was negligible in human plasma, including lipidemia and hemolytic plasma. A simple, efficient and accurate LC–MS/MS method was successfully established and applied to a pharmacokinetic study in healthy Chinese volunteers after a single oral administration of ibuprofen granules.