Resumo O aumento contínuo do uso e liberação de agrotóxicos tem tornado o cenário preocupante, pois a contaminação das águas pode afetar a saúde e o meio ambiente. Neste estudo, um método multiresíduo em água foi otimizado e validado. O método foi desenvolvido utilizando o método QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) seguido de cromatografia líquida acoplada a espectrometria de massa (UHPLC-MS/MS). A validação foi realizada na matriz (água do rio) avaliando à exatidão, precisão, linearidade, limites de detecção (LODs) e limites de quantificação (LOQs). Os LODs ficaram abaixo de 3,03 µg L-1 e os LOQs variaram de 6,25 a 9,18 µg L-1. A exatidão apresentou recuperações de 80 a 117% e o coeficiente de variação para a repetibilidade foi de 0,35-15,71% e de 0,48-7,02% para a precisão intermediária. preocupante ambiente estudo validado Quick, Quick (Quick Easy Cheap Effective Rugged Safe UHPLCMS/MS. UHPLCMSMS UHPLC MS/MS . MS (UHPLC-MS/MS) rio linearidade (LODs LOQs. (LOQs) 303 3 03 3,0 L1 L 1 L- 625 6 25 6,2 918 9 18 9,1 L1. 1. 8 117 0,3515,71% 0351571 0,35 15,71% 0 35 15 71 0,35-15,71 0,487,02% 048702 0,48 7,02% 48 7 02 0,48-7,02 intermediária UHPLCMS UHPLCMS/MS MSMS (UHPLC-MS/MS (LOQs 30 3, 62 2 6, 91 9, 11 3515 0,3515,71 035157 035 0,3 1571 15,71 0,35-15,7 487 0,487,02 04870 048 0,4 702 7,02 4 0,48-7,0 351 0,3515,7 03515 0, 157 15,7 0,35-15, 0,487,0 0487 04 70 7,0 0,48-7, 0,3515, 0351 15, 0,35-15 0,487, 7, 0,48-7 0,3515 0,35-1 0,487 0,48- 0,351 0,35-

Abstract The continuous increase in the use and release of pesticides is worrisome because water contamination can affect health and the environment. This study optimized and validated a multi-residue method in water. The method was developed using the QuEChERS method (Quick, Easy, Cheap, Effective, Rugged, and Safe) followed by ultrahigh- performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS). The validation was performed on the matrix (river water) regarding accuracy, precision, linearity, limits of detection (LODs) and limits of quantification (LOQs). LODs were below 3.03 µg L-1and LOQs were from 6.25 to 9.18 µg L-1. The accuracy (recoveries in the range of 80-117%) and for Inter-day precision, the coefficients of variation ranged from 0.35 to 15.71%, and for Intra-day precision were in the range of 0.48 to 7.02%. environment multiresidue multi residue Quick, Quick (Quick Easy Cheap Effective Rugged Safe ultrahigh UHPLCMS/MS. UHPLCMSMS UHPLC MS/MS . MS (UHPLC-MS/MS) river linearity (LODs LOQs. (LOQs) 303 3 03 3.0 L1and Land L 1and 625 6 25 6.2 918 9 18 9.1 L1. L1 1. 1 L-1 recoveries 80117% 80117 80 117% 117 80-117% Interday Inter day 035 0 35 0.3 1571 15 71 15.71% Intraday Intra 048 48 0.4 702 7 02 7.02% UHPLCMS UHPLCMS/MS MSMS (UHPLC-MS/MS (LOQs 30 3. 62 2 6. 91 9. L- 8011 8 11 80-117 0. 157 15.71 04 4 70 7.02 801 80-11 15.7 7.0 80-1 15. 7. 80-

Abstract Hesperidin is a natural compound which is found in citric fruits and presents antitumor and antimicrobial activities. However, the in vivo efficacy of Hesperidin is reduced due to its low oral bioavailability. Protein-based nanoparticles have been applied to improve biological parameters of drugs and natural compounds. Gliadin is a monomeric protein present in wheat. In this study, gliadin-based nanoparticles containing hesperidin were obtained by desolvation technique and a Taguchi orthogonal array design was employed to optimize the formulation. The independent variables were set as concentration of CaCl2 (0.5; 1 or 2%) and stabilizing agent (Pluronic F68, Tween 80 or sodium caseinate). The dependent variables consisted of mean diameter, polydispersity index, zeta potential, and encapsulation efficiency. The results showed significant effects on the dependent variables when 1% CaCl2 and Pluronic F68 were used. The optimized formulation was coated with chitosan to increase the physical stability of the nanoparticles. The final nanoparticles presented a mean diameter of 321 nm and polydispersity index of 0.217, and spherical shape. After coating, the Zeta potential was +21 mV, and the encapsulation efficiency was 73 %. The in vitro release assay showed that about 98% of the drug was released from the nanoparticles after 48 h. Moreover, the nanoparticles reduced hesperidin cytotoxicity on healthy cells (Vero cells) and improved the cytotoxicity on tumor cells (HeLa, PC-3 and Caco-2 cells). Results showed that the chitosan-coated gliadin nanoparticles are potential carriers for hesperidin delivery for cancer treatment.