Banca de DEFESA: ISABELA DE PAULA LIMA
Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.DISCENTE : ISABELA DE PAULA LIMA
DATA : 18/07/2018
HORA: 10:00
LOCAL: Sala 50 - Pavilhão de Química
TÍTULO:
Bioanalytical method for quantification of Doxycycline in canine plasma: development, validation and application in pharmacokinetic studies.
PALAVRAS-CHAVES:
Doxycycline, sample preparation, pharmacokinetics
PÁGINAS: 118
GRANDE ÁREA: Ciências Exatas e da Terra
ÁREA: Química
SUBÁREA: Química Analítica
RESUMO:
Doxycycline is an antimicrobial agent from the tetracycline family that acts inhibiting the synthesis of bacterial proteins by binding, principally, to the 30S subunits of bacterial ribosomes, preventing the access of the aminoacetyl-tRNA to the receptor site in the mRNA-ribosome complex. It is often the choice for the treatment of canine Ehrlichiosis. Currently, doxycycline is available in the veterinary market under the pharmaceutical forms: tablet and suspension. It is a class well studied, in the literature are easily found articles describing the methods of analysis for determination of the components of this class in human plasma, however, in canine plasma the methods described by HPLC-UV are scarce, having microbiological methods being more used. In this work, a method was developed and validated for the determination of doxycycline in canine plasma. The samples were submitted to liquid-liquid extraction with low temperature partitioning (LLE/LTP) followed by separation by reverse phase liquid chromatography (RP-LC), using as the mobile phase acetonitrile / water adjusted to 2.5 with oxalic acid (80:20 v/v), the gradient flow between 0.8-1.0 mL/min, with ultraviolet (UV) detection at 357 nm. Oxytetracycline was used as internal standard (IS). The validation of the method showed selectivity, sensitivity, absence of matrix and residual effects, and stability. The linearity of the method was established in the range of 0.5-10 μg/mL (r > 0.99), with lower limit of quantification (LLOQ) in 0.5 μg/mL. Intra- and inter-day accuracy presented CV values of less than 20% for LLOQ and 15% for other quality control samples and intra and inter-day accuracy values expressed in RSE, presented in the range of ±20% for LLOQ and ±15% for the other quality control samples. The method was fully validated, taking into account all the parameters of ANVISA's legislation. The methodology was applied for analysis of comparative pharmacokinetics of doxycycline administered orally from two solid dosage forms: chewable tablet and commercial tablet (Doxifin®). Administration of these formulations reached, respectively, blood circulation (Cmax = 1.11 and 1.16 μg/mL), being absorbed (tmax of 240 and 195 minutes) and eliminated (t½ = 1106.24 ± 130.41 and 1685.919 ± 726.44 minutes) rapidly. The similarity in the plasma profiles of the two formulations tested was observed and bioequivalence was confirmed by statistical tests.
MEMBROS DA BANCA:
Presidente - 1700427 - YARA PELUSO CID
Interno - 1177598 - ROSANE NORA CASTRO
Externo à Instituição - LAIS BASTOS DA FONSECA - FIOCRUZ