Plotytsia S. Voltammetric determination of local anaesthetics of amide group with the preliminary derivatization

The thesis deals with the study of the peculiarities of six local anaesthetics voltammetric determination, viz. lidocaine, trimecaine, mepivacaine, bupivacaine, novocaine and benzocaine, by means of different working electrodes. Different approaches to the derivatization of anaesthetics were considered. Amide group is common for anaesthetics and suitable for the derivatization, it is easily oxidized by peroxy acids to the corresponding N-oxide; also primary amino group of novocaine and benzocaine is suitable for the oxidation (chemical and electrochemical) and for the diazotization. Obtained diazo salts of novocaine and benzocaine undergo azo coupling reaction. The corresponding products of anaesthetics oxidation, as well as diazo and azo derivatives of benzocaine and novocaine, are easily electrochemically reduced on a dropping mercury electrode. For the first time, the miniaturized thick-film boron-doped diamond electrode was used for the voltammetric determination of benzocaine. Benzocaine is irreversibly oxidized at this electrode with the occurring of a single peak on the voltammogram in the potential range from +1.0 to +0.8 V; the current linearly depends on the concentration of benzocaine in the wide concentration range, viz. from 1∙10-7 to 2∙10-5 mol/l. The limit of quantification of benzocaine by its oxidation at a diamond electrode by the method of a differential pulse voltammetry is significantly smaller than for many known methods of its determination. The modification of a graphite electrode with polyaniline-based composites was also studied in this work, but it did not lead to the expected results. Based on the obtained results, the new methods have been developed for the determination of anaesthetics in single-component solutions for injections, complex pharmaceuticals (tablets, pastilles, lozenges for sore throat, solutions based on herbal extracts, ointments) and in model samples of human saliva and urine. The new methods of local anaesthetics determination have wide linearity ranges (1.5-2 concentration orders), low quantification limits (at the level of 10-7–10-6 mol/l), sufficient accuracy and selectivity. The validation parameters of new methods are not inferior to the standard methods, and their quantification limits and selectivity prevail over the existing titrimetric techniques; also the new methods are more rapid and cost-effective than chromatographic ones. Methods for the polarographic determination of lidocaine and mepivacaine in injection solutions using the derivatization by Oxone were validated according to the State Pharmacopoeia of Ukraine.