- Co-determination of two antiparasitics drugs by derivative spectrophotometry and its photodegradation studies
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This work proposes a method for the co-determination of praziquantel and fenbendazole in veterinary pharmaceutical formulations (VPF) by second-derivative spectrophotometry at 226.4 nm (Zero-crossing method) and 324.6 nm (Graphic method), respectively. The excipients commonly used in VPF do not interfere. To obtain the optimal determination conditions, studies of solvent and light effects, were performed. The results of the light effects show that the expose of both drugs to indirect light and darkness does not produce any chemical change, since their zero-order spectra remained unchanged during the experiment. However, the exposition to the direct light only affects the fenbendazole. The zero order spectrum of FBZ in EtOH-HCl, present two broad bands (200 to 240 nm and 260 to 330 nm), these signals disappear and appear others totally different, at 230 nm and other with two peaks (285 and 295 nm). The FT-IR spectrum shows characteristics signals of the FBZ structure as the amide-NH group (3336.3 cm-1), this signal disappear indicating the bond break of the amide group caused by the exposition to sunlight for a time. These spectral changes evidenced a structural transformation as a result of photochemical decomposition in acid medium.
- Soto, Cesar,Otipka, Romina,Contreras, David,Yanez, Jorge,Toral, M. Ines
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p. 1824 - 1829
(2014/03/21)
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- The mechanism of decomposition of N-methyl-N-nitrosourea (MNU) in water and a study of its reactions with 2'-deoxyguanosine, 2'-deoxyguanosine 5'-monophosphate and d(GTGCAC)
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The carcinogenicity of N-methyl-N-nitrosourea (MNU) arises, from its ability to methylate DNA, This occurs in an aqueous environment and therefore an appreciation of the mode of decomposition of MNU in water is essential to understanding the mechanism of DNA methylation and its base sequence dependence. The kinetics of MNU hydrolyses are shown to be first order in MNU with a steep rise in rate above pH 8. Using NMR for in situ monitoring of reaction intermediates and products from hydrolyses of [13CO]MNU, [15NH2]MNU and [13CH3]MNU, it is proved that base-induced hydrolysis of MNU is initiated by deprotonation at the carbamoyl group. The critical reactive species are shown to be the methyldiazonium ion (Me-N2+) and cyanate (NCO-). Investigations of reactions of [13CH3]MNU with 2'-deoxyguanosine (dGuo) and 2-deoxyguanosine 5'-monophosphate (dGuo-5P) showed that: a) the site of methylation of dGuo is highly pH-dependent (relatively more N-1 and O6-methylation compared to N-7 occurs at higher pH; b) the principal site of methylation of dGuo-5P by MNU is at phosphate; c) incorporation of deuterium into methyl groups occurs in D2O at higher pH. Methylation of the oligonucleotide d(GT[15N]GCAC) by MNU in D2O showed partial deuteriation of the N7-methyl groups of the guanines, whilst methylation by MNU in water indicated no significant preference for either guanine with respect to N7-methylation.
- Golding, Bernard T.,Bleasdale, Christine,McGinnis, Joseph,Mueller, Susanna,Rees, Hue Thu,Rees, Nicholas H.,Farmer, Peter B.,Watson, William P.
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p. 4063 - 4082
(2007/10/03)
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