RESUMO
A novel water-compatible C60-monoadduct based imprinted micelles was synthesized by the self-assembly of vinylic-C60-monoadduct with sodium dodecylsulfate micellar system, in the presence of chlorambucil as a model template (anticancer drug). After template retrieval with acetonitrile, these imprinted micelles were immobilized at the surface of ionic liquid decorated carbon ceramic electrode. Herein, C60-monoadduct (the head group of micelle) actually served as a nanomediator for electronic transmission across multiple interfaces. Such modification induced electrocatalytic characteristics by decreasing analyte oxidation overpotential and thereby augmented the electrode kinetics. Consequently, the differential pulse anodic stripping transduction was realized to be approximately four-fold as compared to the corresponding electrode modified without C60-monoadduct. This revealed the potential role of fullerene as nanomediator in the signal transduction. Herein, ionic liquids facilitated electron transport by two-fold without any interfacial barrier through carbon layers than that realized with modified ceramic electrodes made in the absence of ionic liquids. A perfect linearity in the current-concentration profile under optimal conditions was observed for the analyte concentration in the range 1.47-247.20ngmL-1, with the detection limits to the tune of 0.36ngmL-1 (S/N=3) in aqueous and real samples.
Assuntos
Técnicas Biossensoriais/métodos , Clorambucila/isolamento & purificação , Técnicas Eletroquímicas/métodos , Fulerenos/química , Clorambucila/química , Micelas , Impressão Molecular , Água/químicaRESUMO
A reversed-phase high-performance liquid chromatographic method is described to distinguish chlorambucil N-oxide from the parent chlorambucil and quantitate both after separation from biological samples. The influence of solvent pH, alcohol, acid and ion-pairing agent on the separation is described. The stability of chlorambucil and its N-oxide in buffers and alcohols, as well as stability during filtration is discussed with potential application for metabolic studies.
Assuntos
Clorambucila/análogos & derivados , Clorambucila/isolamento & purificação , Cromatografia Líquida de Alta Pressão/métodos , Óxidos N-Cíclicos/isolamento & purificação , Acetonitrilas , Álcoois , Animais , Soluções Tampão , Estabilidade de Medicamentos , Etilaminas , Concentração de Íons de Hidrogênio , Metanol , Microssomos Hepáticos/química , Pró-Fármacos/isolamento & purificação , Ratos , Ácido TrifluoracéticoRESUMO
The antitumour agent chlorambucil (4[4-bis(2-chloroethyl)aminophenyl]-butyric acid) is converted by beta-oxidation in vivo into phenylacetic mustard (2[4-bis(2-chloroethyl)aminophenyl]acetic acid). This process may be disadvantageous from a therapeutic viewpoint since the metabolite has half the therapeutic index of the parent drug against the Walker 256 carcinoma in rats. In seeking to retard beta-oxidation, selectively deuterated analogues have been synthesised and administered to rats. Plasma levels of phenylacetic mustard after giving chlorambucil-beta-d2 were lower than those given by unlabelled drug, but the therapeutic activity was not significantly altered by deuteration. A dehydro derivative of chlorambucil was detected as an intermediate in the beta-oxidation pathway. The isotopic compositions of this metabolite, and of recovered chlorambucil, were measured in plasma samples taken after giving labelled chlorambucil (alpha-d2 and beta-d2 variants) to rats. Deuterium was almost totally lost from the alpha-d2 form and from its metabolite after 30 min and partially lost in 10 min. The beta-d2 variant and its dehydro-derivative retained the label. Possible mechanisms for deuteration loss are discussed. The design of novel analogues, based on these metabolic studies, is proposed.
