Rusu Aura1*, Popescu Gabriel-Cosmin2, Imre Silvia3, Ion Valentin3, Vancea Szende4, Grama Anda-Lavinia5, Kelemen Hajnal1, Hancu Gabriel1
1 University of Medicine and Pharmacy of Tîrgu Mureş, Faculty of Pharmacy, Department of Pharmaceutical Chemistry
2 University of Medicine and Pharmacy of Tîrgu Mureş, Faculty of Pharmacy, student
3 University of Medicine and Pharmacy of Tîrgu Mureş, Faculty of Pharmacy, Department of Analytical Chemistry
4 University of Medicine and Pharmacy of Tîrgu Mureş, Faculty of Pharmacy, Department of Physical Chemistry
5 University of Medicine and Pharmacy of Tîrgu Mureş, Faculty of Pharmacy, Department of General and Inorganic Chemistry
Objective: Silver complexes of antibacterial quinolones have the potential advantage of combining the antibacterial activity of silver and fluoroquinolones. The objective of our study was the preparation and the preliminary physico-chemical characterization of a silver complex with ofloxacin.
Methods: To achieve our goals several spectroscopic methods (ultraviolet spectrophotometry, mass spectrometry, and Fourier transform infrared spectroscopy) and thermal methods (differential scanning calorimetry and thermogravimetric analysis) were used in order to elucidate the chemical structure of the complex.
Results: Using mass spectrometry we established the stoichiometric ratio silver:ofloxacin as 1:2. Experimental data suggest a particular coordination for ofloxacin, as a monodentate ligand, in the formation of a complex with silver, through the nitrogen atom from the methyl-piperazine cycle.
Conclusions: The obtained complex has a chemical structure likely [Ag(Ofloxacin)2]NO3, requiring evaluation through other physico-chemical methods.
University of Medicine and Pharmacy Târgu Mureş, Faculty of Pharmacy, Department of Pharmaceutical Chemistry
Background: Quinolones are synthetic antibacterial agents, with a 4-oxo-1,4-dihydroquinolinic structure, which is based on the nalidixic acid model. The 4-oxo and 3-carboxyl groups confer quinolones excellent chelatation properties with metallic ions.
Aim: To highlight a few theories regarding the complexation phenomenon of quinolones.
Methods: Complexes with metallic ions have been characterized (stoichiometry, in vitro physical-chemicals properties, stability studies, and behavioral studies in different biological mediums).
Results: New availabilities have been identified: bioavailability of the complexed quinolones and formulation of new pharmaceutical products with a superior bioavailability and therapeutic effect; the antimicrobial activity of quinolone complexes; quinolone complexes as antitumor drugs with the aim of obtaining less toxic compounds; understanding the mechanism of action of quinolones, which is a challenge especially regarding their selectivity at the bacterial DNA level; development of new determination methods, based on the complexation of quinolones with metallic ions.
Conclusions: The 21st century may provide new useful therapeutic aspects on the basis of complexation between quinolones and metals.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Medicine and Pharmacy Targu Mures, Romania
Background: In this work the applicability of capillary zone electrophoresis for the separation of quinolones from different generations has been studied.
Objective: Our aim was to develop a capillary electrophoretic method for the simultaneous separation of four quinolones and also to optimize the analytical conditions.
Material and methods: Capillary electrophoresis (CE) is a family of related techniques that use narrow-bore fused-silica capillaries to perform high efficiency separations of both small and large molecules. For this we chose four quinolones: a naftiridine derivate (nalidixic acid), a pyrido-pyrimidine derivate (pipemidic acid) and two second generation fluoroquinolones with different structures (ciprofloxacin, ofloxacin).
Results: A fast and reliable method has been developed, using a separation buffer composed of 40 mM natrium tetraborate and 5% methanol as organic modifier, with whom we achieved the separation of the studied quinolones in less than 10 minutes.
Conclusions: CE proved to be an efficient tool in the separation of quinolones from different generations.
1 Pharmafarm, Tîrgu Mureş, Romania
2 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Medicine and Pharmacy, Tîrgu Mureş, Romania
Background: Penicillins and fluoroquinolones are two of the most extensively utilized class of antibacterial substances. Taking into account the importance of these compounds in the human and veterinary antibacterial therapy, identification and separation of these compounds in different complex matrices represent a necessity and also a challenge.
Objective: The aim of our study was to elaborate an alternative separation technique, suitable for the identification and separation of four penicillin derivatives – amoxicillin, ampicillin, benzylpenicillin and oxacillin – and two fluoroquinolones: ciprofloxacin and norfloxacin, and to optimize the analytical conditions.
Material and methods: MEKC proved to be the appropriate method of analysis for the separation of the studied compounds. The CE experiments were conducted on the Agilent 6100 CE System; the data were recorded and processed with Agilent Chemstation software.
Results: An optimum separation was achieved using a buffer solution containing 25 mM sodium tetraborate, 100 mM sodium dodecyl sulfate and 100 mM boric acid. The migration order of the six compounds was: amoxicillin, ampicillin, benzylpenicillin, oxacillin, ciprofloxacin and norfloxacin. The analytical performance of the method was evaluated by calculating the standard deviation for the peak area and also by checking the linearity of the determination.
Conclusions: The proposed method proved to be an efficient and useful tool in the separation of the studied substances and can find useful applications in the analysis of the studied substances from environmental samples.
Rusu Aura1*, Imre Silvia2, Mircia Eleonora3, Hancu Gabriel1
1 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Medicine and Pharmacy, Tîrgu Mureş, România
2 Department of Analytical Chemistry and Drug Analysis, Faculty of Pharmacy, University of Medicine and Pharmacy, Tîrgu Mureş, România
3 Department of Organic Chemistry, Faculty of Pharmacy, University of Medicine and Pharmacy, Tîrgu Mureş, România
Objective: Antibacterial quinolones represent an important class of pharmaceutical compounds that are widely used in therapy. Analytical methods that rely on their property to absorb light in the UV range are commonly used for their analysis. In the current study we present an interpretation of the relationship between chemical structure – UV spectra based on the comparative examination of UV spectral behavior of the eighteen quinolone derivatives and four model compounds.
Methods: Eighteen quinolone derivatives and four model compounds were selected and their UV spectra were recorded in different solvents (methanol, 0.1M HCl, 0.1M NaOH).
Results: The studied compounds show three absorption maximum values located around 210-230 nm, 270-300 nm and 315-330 nm values. A general characteristic was observed as the absorption bands exhibited both hypsochrome and bathochrome shifts, by comparison in different solvents. Most commonly we observed a slight hypsochrome shift at acidic pH (protonated form prevails) and basic pH (anionic form prevails). The structural differences are reflected in changes of UV spectra only when there are auxochrom substituents or different basic substituents are present in the quinolones structure.
Conclusions: The correlations between the chemical structure of quinolone derivatives and their UV spectra using model compounds were established. This study provides useful information that can be used successfully in various UV spectrophotometric analysis methods or in more complex analytical methods using UV detection, and also in pharmacodynamic and kinetic studies.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Medicine and Pharmacy, Tîrgu Mureș, Romania
Introduction: Antibacterial quinolones class comprises a series of synthetic antibacterial agents, following the model of nalidixic acid. Because of their common 6-fluorosubtituent on the quinolone ring, fluroquinolones are the most potent analogues with extended spectrum of activity and great pharmacokinetic properties. The applicability of capillary zone electrophoresis for the separation of fluoroquinolones in acidic background electrolyte has been studied, our aim being the development of a capillary zone electrophoresis method for the simultaneous separation of six fluoroquinolones and also to optimize the analytical conditions. The six studied fluoroquinolones were ciprofloxacin, enoxacin, enrofloxacin, moxifloxacin, ofloxacin and sarafloxacin.
Material and methods: Preliminary, we studied the electrophoretic behavior of six fluoroquinolones in an acidic pH, which highlighted the possibility of developing a separation method in this area of pH. Electrophoretic parameters influencing separation performance
were studied and optimized.
Results: A fast and reliable method has been developed, using a background electrolyte containing 100 mM phosphoric acid and the following conditions: applied voltage: + 25 kV, temperature: 20°C, injection pressure 30 mbar – 5 sec, UV detection at 280 nm, capillary: 60 cm (52 cm effective length) x 50 μm, analyte concentration: 167 μg/ml. The separation of the studied fluoroquinolones was achieved in less than 8 minutes.
Conclusions: Capillary zone electrophoresis using an acidic background electrolyte proved to be an efficient tool in the separation of fluoroquinolones from different generations. Also the proposed methods are particular environment-friendly replacement and improvement of a common high performance liquid chromatography determination with rapid analysis time without using any organic solvents.