ОРИГИНАЛЬНЫЕ СТАТЬИ
УДК 543
ANALYTICAL DETERMINATION OF NIMESULIDE AND OFLOXACIN IN PHARMACEUTICAL PREPARATIONS USING SQUARE-WAVE VOLTAMMETRY
© 2014 Francisco W. P. Ribeiro*, Thisiania R. V. Soares*, Sameque do N. Oliveira*, Luisa C. Melo*, Janete E. Soares**, Helena Becker*, Djenaine De Souza***, Pedro de Lima-Neto*, Adriana N. Correia*
*Departamento de Química Analítica e Físico-Química, Centro de Ciencias, Universidade Federal do Ceará, Bloco 940 Campus do Pici 60455-970, Fortaleza — CE — Brazil **Departamento de Farmácia, Faculdade de Farmácia, Odontologia e Enfermagem, Universidade Federal do Ceará, Rua Capitao Francisco Pedro, 1210Rodolfo Teófilo 60430-370, Fortaleza — CE — Brazil
***Campus de Patos de Minas — Instituto de Química — Universidade Federal de Uberlandia Av. Getúlio Vargas, 230 Centro,
CEP 38700-126 — Patos de Minas — MG — Brazil Received 09.02.2012; in final form 13.02.2013
The electrochemical behaviour and analytical detection procedure for nimesulide (NIM) and ofloxacin (OFX) and their assay in commercial formulations were evaluated using square-wave voltammetry (SWV) combined with a hanging mercury drop electrode (HMDE). All experimental and voltammetric conditions were previously optimized to obtain the best analytical signal in terms of intensities and profile of the reduction peaks. For NIM, the peak currents were related to the one-electron reduction of a nitro group to a stable radical anion, which is followed by a one-electron transfer and a protonation step with a consequent formation of a nitrosoanion. The voltammetric results indicated that the mechanism of OFX involved the transfer of two electrons and two protons in a totally irreversible reduction related to the conversion of a ketone group to an alcohol group. Analytical parameters such as linearity range, equations of the analytical curves, correlation coefficients, detection and quantification limits, recovery efficiency, and relative standard deviation for repeatability and reproducibility experiments were compared to similar results obtained by the use of UV-Vis spectrophotometry, and the results showed that the voltammetric procedure using HMDE is suitable to determine pharmaceutical compounds in complex samples. The applicability of the proposed procedure was tested on pharmaceutical formulations of NIM and OFX by observing the stability, specificity, recovery and precision of the procedure in tablets, oral solution and ophthalmic solution.
Keywords: nimesulide, ofloxacin, square-wave voltammetry, pharmaceutical formulations, electrochemical behaviour.
DOI: 10.7868/S0044450214010071
The arrival of a great number of generic drugs, and, in particular, the appearance of various pharmaceutical laboratories, which are responsible for the research, production, distribution and commercialization of pharmaceutical compounds of various classes and in different dosage forms, has created the necessity of the development of precise and sensitive analytical procedures for drug control laboratories to quantify compounds in commercial formulations, and also to determine the degradation products and the presence of impurities. Moreover, the analytical determination of pharmaceutical compounds is very important for optimum therapeutic concentrations, while minimizing the risk of toxicity.
Among the commercial pharmaceutical compounds that require rigorous quality control, mainly by the low therapeutic dosage employed, nimesulide (NIM) and ofloxacin (OFX) have been evaluated using different analytical procedures. NIM {N-(4-nitro-2-phenoxyphenyl) methane sulphonamide} is a nonsteroidal anti-inflammatory drug, the inadequate use of which may cause gastrointestinal ulcers. OFX {(±)-9-fluoro-2,3-dihydro-3-ethyl)10(4-methyl)-1-piper-ozinyl)-7-oxo-7H-pyrio[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid} is an anti-microbial agent widely used in the treatment of infections [1].
High-performance liquid chromatography is one of the main techniques used in determining the purity of batches of NIM and OFX in commercial formula-
67
5*
tions [2—4]. Meanwhile, capillary zone electrophoresis [5—8], and spectroscopy techniques [9—11] are frequently used for analytical purposes. These procedures, even though they exhibit highly satisfactory sensitivity for analytical quantification of pharmaceutical compounds, require, in some cases, a prior step of extraction or extensive reagents and equipment [12, 13].
In recent years some procedures surrounding elec-troanalytical techniques have also been employed to determine NIM and OFX in commercial formulations [14, 15]. These techniques are powerful and versatile analytical tools, due to certain convenient features, including high sensitivity, accuracy, precision, and simplicity of experimental procedures, as well as a large linear dynamic range, with relatively low costs of instrumentation and short duration of analysis [16].
Among electroanalytical techniques, square-wave voltammetry (SWV) has proved to be an extremely sensitive method for the detection of pharmaceutical and other compounds, both organic and inorganic [17]. Moreover, SWV has been widely used to obtain information concerning the kinetic and charge-transfer mechanisms involved in pharmaceutical compounds and other biologically significant molecular reactions [18, 19]. This information is most relevant in the evaluation of the redox properties of these compounds, identification of the intermediate reactive species, elucidation of action mechanisms and metabolic events of drugs, and also in the supply of information about redox properties in the human organism, since the reactions in humans are very similar to the redox process that occurs when electroanalytical techniques are employed [20].
Regarding the evaluation of the electrochemical behaviour and the quantification of pharmaceutical compounds by electroanalytical techniques, metallic and carbon-based electrodes present excellent mechanical and electrical properties, and impermeability to gases [21]. Moreover, the use of modified electrodes that have already been used as working electrodes can promote the suitable selective detection of pharmaceutical compounds [22]. In all published works, it was observed that many pharmaceutical compounds are suitable electron donors or receptors; they can be oxidized or reduced, thus producing currents that are proportional to the analytical concentration.
However, the major limitations in the use of these electrode surfaces are related to the adsorption of the reagents from the measuring solution or the resultant products of the electrochemical reactions, which sometimes produces low sensitivity and reproducibili-ty of the electrochemical responses. In this context, the mercury electrodes offer the electronic control of the formation of the electrodic surface, which offers a highly reproducible, readily renewable, smooth and stable surface [16].
In this study, the use of the hanging mercury drop electrode (HMDE) combined with square-wave volta-
mmetry (SWV) is explored in order to establish an appropriate and efficient methodology for the analytical determination of NIM and OFX in pharmaceutical formulations, and also to study electrochemical behaviour by the appropriate use of a well-developed theoretical model of the SWV technique.
EXPERIMENTAL
Reagents and equipment. All voltammetric measurements were taken with a potentiostat (Autolab PGSTAT 30, Metrohm-Eco Chemie) controlled by a personal computer, using GPES version 4.9 software (General Purpose Electrochemical System, Metro-hm-Eco Chemie). A conventional cell with a three-electrode system, consisting of an Ag/AgCl/saturated Cl- electrode as the reference electrode, a graphite rod as the auxiliary electrode, and a hanging mercury drop electrode (663 VA Stand from Metrohm, surface area 0.52 mm2) as a working electrode.
For UV-Vis measurements, a Varian spectrophotometer model Cary 1E was employed, with the wavelength operating from 190 to 900 nm. A quartz cell with an optical path of 1 cm was employed in these measurements.
A Micronal B474 pH meter equipped with a 3.0 M Ag/AgCl/KCl-glass combined electrode was used to adjust the pH values. All solutions were prepared with water purified by a Milli-Q system (Millipore Corp.).
Stock solutions of1.0 x 10-3 M of USP-grade NIM and OFX were prepared daily by dissolving suitable quantities in water and pure ethanol, respectively, which were then stored in a dark flask and kept in a refrigerator to prevent degradation.
0.04 M of Britton-Robinson (BR) buffer, prepared as described in a previous paper [23], was used as the supporting electrolyte and the pH was adjusted to the desired value by adding suitable amounts of 0.2 M NaOH stock solution.
Working procedure. All measurements were carried out under ambient conditions. The appropriate solutions were transferred to the electrochemical cell and the optimization of the analytical procedure for SWV was carried out following a systematic study of the experimental parameters that affect the responses, such as the pH of the medium, the pulse potential frequency related to total pulse duration, the amplitude of the pulse, and the height of the potential step or scan increment. All parameters were properly optimized since their values exert high influence on the sensitivity of voltammetricanalysis [17, 18]. The mentioned parameters were optimized in relation to the maximum value ofpeak current and the maximum selectivity (half-peak width).
To accomplish the above, the working electrode was placed in the measuring cell filled with 20 mL of a BR buffer solution containing a known concentration of each pharmaceutical compound, and the experi-
mental and voltammetric parameters were subsequently studied. Before each experiment, a stream of N2 was passed through the solution for 10 min. Following the oxygen removal, negative scans were made in the interval of 0.1 to —1.2 V vs. Ag/AgCl/satur
Для дальнейшего прочтения статьи необходимо приобрести полный текст. Статьи высылаются в формате PDF на указанную при оплате почту. Время доставки составляет менее 10 минут. Стоимость одной статьи — 150 рублей.