Orientador: Marcos Nogueira Eberlin / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Química / Made available in DSpace on 2018-08-22T00:48:57Z (GMT). No. of bitstreams: 1 Fernandes_RaquelMariaTrindade_D.pdf: 2391491 bytes, checksum: e0ced742cb6fd1e2732195078347fd99 (MD5) Previous issue date: 2012 / Resumo: O presente trabalho descreve a utilização de polímeros de impressão molecular (MIP) no preparo de amostra para a extração seletiva de fármacos em matrizes biológicas com determinação por LC-MS/MS e MS/MS. Inicialmente foi sintetizado e caracterizado um MIP seletivo a omeprazol, sendo o mesmo empregado na extração com fase sólida molecularmente impressa (MISPE) de omeprazol em amostras de plasma humano, seguido de determinação por LC-MS/MS. A metodologia foi validada por meio do estudo dos parâmetros: precisão (repetibilidade e precisão intermediária), exatidão (recuperação), curva analítica, intervalo de linearidade, limite de detecção ¿ LD e limite de quantificação ¿ LQ, e seletividade. O limite de quantificação obtido foi de 5 ng mL. Posteriormente, foi sintetizado e caracterizado um MIP seletivo a cocaína, sendo este empregado na extração em fase sólida molecularmente impressa (MISPE) online de cocaína em amostras de urina de usuários de drogas, seguido da quantificação por MS/MS. O limite de quantificação obtido foi de 10 ng mL. A seletividade do método foi avaliada pelo estudo de adsorção de metabólitos (benzoilecgonina e cocaetileno) e interferente (lidocaína) pelo polímero sintetizado e posterior determinação por MS/MS. / Abstract: The present work describes the applications of molecularly imprinted polymers (MIP) in sample preparation for the selective extraction of drugs in biological matrices by LC-MS/MS and MS/MS. Initially a MIP selective for omeprazolewas synthesized and characterized. It was used in molecularly imprinted solid phase extraction (MISPE) of omeprazole from human plasma samples, followed by LC-MS/MS determination. The methodology was validated by studying the parameters: precision (repeatability and intermediate precision), accuracy (recovery), calibration curve, linear range, detection limit - LOD and quantification limit - LOQ, and selectivity. The quantification limit was 5 ng ml. Subsequentlya MIP selective for cocaine was synthesized and characterizedwhich was used in online molecularly imprinted solid phase extraction (MISPE) for cocaine in urine samples of drug users, followed by quantification by MS / MS. The quantification limit was 10 ng mL. The selectivity of the method was evaluated by studying the adsorption of metabolites (benzoylecgonine and cocaethylene) and an interferent (lidocaine) by the synthesized polymer with subsequent determination by MS / MS. / Doutorado / Quimica Analitica / Doutora em Ciências

Modified-release oral drug delivery dosage forms are widely used in the pharmaceutical field to overcome all the potential issues imposed by the physiological variabilities of the gastrointestinal tract as well as to maintain drug concentrations within the therapeutic window. In the market, they are available only as solid dosage forms such as capsules or tablets. The development of a liquid oral dosage form with modified-release properties has been keenly awaited. This form could increase the compliance of patients with a swallowing impairment (i.e. paediatric, older or critically ill patients) and, consequently, the efficacy of the therapeutic treatment. In this study, a new technology has been developed that consists of multi-layered particles suspended extemporaneously in a syrup. Omeprazole and budesonide have been employed as model drugs. The coating procedure was optimized to obtain a yield of minimum 90% w/w and a median diameter below 500 µm. Once the final suspension is prepared extemporaneously, it presents sufficient stability to guarantee the administration of multiple doses filled into a syrup bottle and kept for a limited storage time at room temperature (e.g. up to 10 doses to be administered within 10 days). / Doctorat en Sciences biomédicales et pharmaceutiques (Pharmacie) / info:eu-repo/semantics/nonPublished