Acidity constants of cefetamet, cefotaxime and ceftriaxone; the effect of the substituent at C3 position.

Ionization constants of three cephalosporin antibiotics, cefetamet (CEF), cefotaxime (CFX) and ceftriaxone (CFTR) are determined using pH-potentiometric titrations at I=0.1 M (NaCl) and t=25 degrees C. Cefetamet and cefotaxime have three ionization groups: carboxylic, amide and aminothiazole. Besides those three, ceftriaxone possesses an hydroxytriazinone group as new and additional ionization center. In acid medium two overlapping acid-base processes are occurring with acidity constants being: pK1 2.93 (COOH) and pK2 3.07 (aminothiazole) for cefetamet, and pK1 2.21 (COOH) and pK2 3.15 (aminothiazole) for cefotaxime. In the case of ceftriaxone the situation is even more complicated, three overlapping processes coexist with pK1 2.37 (COOH), pK2 3.03 (aminothiazole) and pK3 4.21 (hydroxytriazinone). Protolysis of amide group is happening in the alkaline medium as completely separated process from those in acid medium. The acidity constants which correspond to amide group are pK3 10.65 (CEF), pK3 10.87 (CFX) and pK4 10.74 (CFTR). The influence of the C3 substituent on the dissociation process of the neighboring ionization group, particularly carboxylic group, was considered. The differences in acidity of CEF, CFX and CFTR (pK1: 2.93, 2.21 and 2.37, respectively) are likely to be caused by the stereoelectronic properties of substituents in the beta-position to the carboxylic group due to the combined inductive, hyperconjugative and resonance effects.

Determination of the ionization constants of 4-iodo-2,6-dimethylphenylcarbamoylmethyl iminodiacetic acid.

In order to develop a radiopharmaceutical for hepatobiliary scintigraphy with better hepatobiliary properties new ligand for complexation of 99mTc, 4-iodo-2,6-dimethylphenylcarbamoylmethyl iminodiacetic acid (METHYLIODIDA), was synthesized. Acid-base equilibria of METHYLIODIDA were studied potentiometrically, because these data are important for determination of complex formation conditions. It was established that METHYLIODIDA undergoes a complex acid-base equilibrium due to its zwitterionic nature and four proton-binding sites. The stoichiometric ionization constants were determined at 25 degrees C and constant ionic strength 0.1M (NaClO(4)): pK1=1.7+/-0.1; pK2=2.44+/-0.07; pK3=6.29+/-0.02 and pK4=10.91+/-0.06, respectively.

Spectrophotometric and HPLC determination of fleroxacin in tablets.

The paper describes and compares spectrophotometric and HPLC determination of fleroxacin in commercial tablets. The optimum conditions for spectrophotometric assay were found to be at pH < 3.5 (0.1 M HCl) at a wave length of 286 nm. HPLC analysis was carried out on a Beckman ODS 5 microns column in a pH 3 phosphoric acid solution (detector wave length 254 nm).

Voltammetric methods for analytical determination of fleroxacin in quinodis tablets.

The direct current (dc) and differential pulse (dp) polarographic reduction of fleroxacin was done in a wide pH range from 2.48 to 13.00. The appropriate buffer choice was made for its dp polarographic determination in a range from 1.845 to 16.926 microg /ml, at pH 8.50. The adsorptive properties of fleroxacin were investigated in order to achieve an increase in sensitivity and a possibility of fleroxacin determination by applying the adsorptive stripping voltammetric method. The adsorptive processes at the hanging mercury drop electrode were investigated in Britton-Robinson and borate buffers. Adsorptive preconcentration followed by differential-pulse cathodic stripping showed one wave at approximately - 1.1 V being the most sensitive for analytical determination of fleroxacin. Two linear ranges were obtained, the first one from 18.465 to 258.51 ng/ml, and the second one from 3.693 to 18.465 ng/ml.

Electrochemical study of cefetamet-Na and its polarographic determination.

Polarographic behavior of cephalosporin cefetamet-Na (Cef-Na) in aqueous solutions of pH ranging from 1.7 to 12.5 was investigated by applying direct current (dc) polarography, differential pulse polarography (dpp), alternating current (ac) polarography, cyclic voltammetry and electrolysis at constant potential. The characteristics of the corresponding electrode reaction are presented and discussed. The electrode reaction was found to be affected by strong adsorption, strongly and slightly pronounced in acidic and alkaline media, respectively. The methoxyimino group electroreduction was carried out and the mechanistic scheme was suggested. In addition, a sensitive dpp method was proposed for analytical determination of a very low concentrations of Cef-Na.

Study of acid-base equilibria of fleroxacin.

The acid-base equilibria of fleroxacin were studied by means of potentiometry and spectrophotometry. It was established that fleroxacin undergoes a complex acid-base equilibrium due to its zwitterionic nature and two proton-binding sites of similar acidity. The stoichiometric equilibrium constants were determined at 25 degrees C and constant ionic strength 0.1 M (NaCl). The acidity constants pK1 = 5.59 +/- 0.01 and pK2 = 8.08 +/- 0.04 were found by potentiometry, and pK1 = 5.61 +/- 0.03 and pK2 = 8.11 +/- 0.06 by spectrophotometry. The distribution diagram of the corresponding ionic species is given.

Spectrophotometric and polarographic investigation of the Ofloxacin-Cu(II) complexes.

By means of spectrophotometric methods it was found that ofloxacin reacts with copper(II) ions to form complexes with molar ratios of ofloxacin: Cu(II) of 1:1 at pH 4.00, 2:1 at pH 7.02 and 3:1 at pH 8.30. The stability constants of the complexes were determined. The formation of ofloxacin:Cu(II) 1:1 and 3:1 complexes was confirmed by a polarographic method and the corresponding overall stability constant was evaluated.

Differential pulse polarographic determination of nizatidine in pharmaceutical formulations.

A sensitive dp polarographic method was applied to the analytical determination of nizatidine, a new histamine H2-receptor antagonist. Determination was performed in Britton-Robinson buffer, at pH approximately equal to 3, ionic strength mu = 0.2. Linear dependence was achieved in a concentration range of 1.33 to 165.72 micrograms/ml for different sensitivities. The method proposed was applied to the determination of nizatidine in capsules and injections.

Polarographic and potentiometric investigation of Co(II) complexes with 5-hydroxytryptophan.

The formation of the complexes between Co(II) and 5-hydroxytryptophan has been studied by means of polarographic and potentiometric methods. The real stability constants of mono and bis-chelato complexes of Co(II) with 5-hydroxytryptophan, obtained by polarographic method, in Britton-Robinson buffer were found to be, log beta 1 = 4.98 and log beta 2 = 8.45. By applying the potentiometric method, in aqueous medium of ionic strength mu = 0.2, the stability constants, log beta 1 = 4.42 and log beta 2 = 8.57 were obtained. The complexes defined by polarographic method have been used in a purpose of analytical determination of 5-hydroxytryptophan.