34604-55-2Relevant articles and documents
Mechanism of aromatic hydroxylation of lidocaine at a Pt electrode under acidic conditions
Gul, Turan,Bischoff, Rainer,Permentier, Hjalmar P.
, p. 636 - 641 (2017)
Aromatic hydroxylation reactions, which are mainly catalyzed by cytochrome P450 (CYP) enzymes in vivo, are some of the most important reactions of Phase I metabolism, because insertion of a hydroxyl group into a lipophilic drug compound increases its hydrophilicity and prepares it for subsequent Phase II metabolic conjugation reactions as a prerequisite to excretion. Aromatic hydroxylation metabolites of pharmaceuticals may be obtained through various synthetic and enzymatic methods Electrochemical oxidation is an alternative with advantages in terms of mild reaction conditions and less hazardous chemicals. In the present study, we report that aromatic hydroxylation metabolites of lidocaine can be readily obtained electrochemically under aqueous acidic conditions at platinum electrodes. Our results show that the dominant N-dealkylation reaction can be suppressed by decreasing the solution pH below 0.5 resulting in selective 3-hydroxylidocaine, which is an in vivo metabolite of lidocaine. Experiments in 18O labelled water indicated that water is the primary source of oxygen, while dissolved molecular oxygen contributes to a minor extent to the hydroxylation reaction.
Electrochemical oxidation by square-wave potential pulses in the imitation of oxidative drug metabolism
Nouri-Nigjeh, Eslam,Permentier, Hjalmar P.,Bischoff, Rainer,Bruins, Andries P.
experimental part, p. 5519 - 5525 (2012/02/15)
Electrochemistry combined with mass spectrometry (EC-MS) is an emerging analytical technique in the imitation of oxidative drug metabolism at the early stages of new drug development. Here, we present the benefits of electrochemical oxidation by square-wa
Simultaneous quantitation of lidocaine and its four metabolites by high-performance liquid chromatography: Application to studies on in vitro and in vivo metabolism of lidocaine in rats
Kawai,Fujita,Suzuki
, p. 1219 - 1224 (2007/10/02)
A convenient and sensitive high-performance liquid chromatographic assay for the simultaneous quantitation of lidocaine and its four metabolites has been developed. The samples containing lidocaine and its metabolites were eluted from a microparticulate octadecylsilane column using a mobile phase of 0.1 M phosphate buffer (pH 3.0) containing 10% acetonitrile. This method was applied to studies on in vitro metabolism and in vivo pharmacokinetics of lidocaine in rats. Kinetic studies of in vitro microsomal metabolism of lidocaine indicated that the apparent K(m) and V(max) for aromatic hydroxylation were smaller than those for N-deethylation. Lineweaver-Burk plots of the N-deethylation of lidocaine and those of its two primary metabolites indicated that at least two isozymes are taking part in these reactions. In in vivo lidocaine pharmacokinetics, the area under the blood concentration-time curve for the monodeethylated product, ω-ethylamino-2,6-dimethylacetanilide (1), varied considerably depending on the route of administration.
