In this work a method for determination of canagliflozin and its degradation products by HPLC with UV and MS detector was developed. The developed method was used to study the forced degradation of canagliflozin and to investigate the major degradation products resulting from exposure of canagliflozin to oxidative stress. Canagliflozin is a phenolic glycoside derivative and a glucose-sodium transporter 2 inhibitor that stimulates urinary glucose excretion by suppressing glucose reabsorption from the proximal tubule in the kidneys. Canagliflozin is used to control blood glucose levels in patients with type 2 diabetes. In an optimized method, an Agilent Poroshell 120 SB-Aq (2.1 × 100 mm, 2.7 µm) column was used and a mixture of buffer (10mM HCOOH adjusted with ammonium hydroxide to pH 3.5) and acetonitrile as a mobile phase. The method validation included testing of accuracy, repeatability, the limit of detection and quantification, linearity and linear dynamic range, the robustness of the method, and testing of sample stability. The limit of detection of the method was 8.9·10-5 mg ml-1 (2.0·10-7 mol l-1 ) and the limit of quantification was 3.0·10-4 mg ml-1 (6.8·10-7 mol l-1 ). At a concentration of 0.3 mg ml-1 , the repeatability (n = 7) was 0.17 % and 0.75 % for the retention time and the peak...

Submitted by Erika Demachki (erikademachki@gmail.com) on 2017-05-05T18:36:49Z No. of bitstreams: 2 Dissertação - Luciana de Souza Barbosa - 2015.pdf: 4757688 bytes, checksum: fc96a42c90e69175023de9611123a61e (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2017-05-09T15:24:36Z (GMT) No. of bitstreams: 2 Dissertação - Luciana de Souza Barbosa - 2015.pdf: 4757688 bytes, checksum: fc96a42c90e69175023de9611123a61e (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2017-05-09T15:24:36Z (GMT). No. of bitstreams: 2 Dissertação - Luciana de Souza Barbosa - 2015.pdf: 4757688 bytes, checksum: fc96a42c90e69175023de9611123a61e (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2015-03-27 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Brazil has the greatest biodiversity in the world, and the plants are major sources of active molecules, having wide structural diversity. Among the domains found in Brazil, the Cerrado is a great source of medicinal plants with biological activities, and promising for the identifi-cation of bioactive molecules. In this context, studies on species of the Cerrado, can signifi-cantly contribute to the development and preservation of this biome. The species Kielmeyera coriacea (Calopyllaceae) is popularly known as pau-santo, being native to the Brazilian cen-tral plateau region. It is used in popular medicine, mainly for gastritis, anemia and leukemia, as reported in ethnobotanical interviews conducted in this study. The chemical study of K. coriacea leaves afforded the substances lupeol, lupenone, β-amyrin, cis and trans-p-coumaric acid and flavonoid quercetin, which was evaluated against the cathepsin V (CatV) and has a high inhibitory potential, had its IC50 assessed, with a value of 2.2 μM. The leaves extract (LE) and fractions originating from the liquid-liquid partition K. coriacea were also tested against cathepsins, and the LE showed the most satisfactory results against CatV, inhibiting the activity by 98%; LE was also tested against the ulcerogenic action, with concentrations of 200 and 300 mg.kg-1, and showed significant inhibition of ulcerative lesions. For antimicrobi-al evaluation, LE showed antimicrobial activity against the fungi Candida albicans, C. tropi-calis and C. glabrata (MIC of 31,25 μg/mL, 62,5 μg/mL e 7,81 μg/mL). Therefore, this re-search made possible the correlation ethnobotanical and scientific data, and contributed with relevant information of chemical-biological character of K. coriacea. / O Brasil possui a maior biodiversidade do mundo, e as plantas são fontes importantes de mo-léculas ativas, possuindo ampla diversidade estrutural. Dentre os domínios encontrados no Brasil, o Cerrado apresenta uma grande fonte de plantas medicinais com atividades biológi-cas, sendo promissor para a identificação de moléculas bioativas. Neste contexto, estudos so-bre espécies pertencentes ao Cerrado podem contribuir significativamente para a valorização e conservação deste domínio. A espécie Kielmeyera coriacea (Calopyllaceae) é conhecida po-pularmente como pau-santo, sendo nativa da região do planalto central brasileiro. É uma es-pécie muito utilizada na medicina popular, majoritariamente para gastrite, anemia e leucemia, conforme relatado nas entrevistas etnobotânicas realizadas neste estudo. Com a realização do estudo químico das folhas de K. coriacea, identificou-se as substâncias lupeol, lupenona, β-amirina, os ácidos cis e trans-p-cumárico e o flavonoide quercetina, o qual foi avaliado frente à catepsina V (CatV) e por apresentar um potencial inibitório elevado, teve seu IC50 avaliado, apresentando um valor de 2,2 μM. O extrato etanólico das folhas (EF) e frações oriundas da partição líquido-líquido de K. coriacea também foram avaliados frente às catepsinas, e o re-sultado mais expressivo para EF foi frente à CatV, inibindo a atividade da mesma em 98%; EF também foi testado frente à ação ulcerogênica, apresentando, nas concentrações de 200 e 300 mg.kg-1, uma inibição significativa das lesões ulcerativas. Em relação à avaliação antimi-crobiana, EF apresentou atividade antimicrobiana frente aos fungos Candida albicans, C. tro-picalis e C. glabrata (CIM de 31,25 μg/mL, 62,5 μg/mL e 7,81 μg/mL). Portanto, a realização deste trabalho tornou possível a correlação de dados etnobotânicos com científicos, além de contribuir com informações relevantes de caráter químico-biológico sobre K. coriacea.