Predrag Djurdjevic

Fluorescence reaction and complexation equilibria between norfloxacin and aluminium (III) ion in chloride medium

Abstract Norfloxacin, 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinoline carboxylic acid (NORH), reacts with aluminium(III) ion forming the strongly fluorescent complex [Al(HNOR)] 3+ , in slightly acidic medium. The complex shows maximum emission at 440 nm with excitation at 320 nm. The fluorescence intensity is enhanced upon addition of 0.5% sodium dodecylsulphate. Fluorescence properties of the Al-NOR complex were used for the direct determination of trace amounts of NOR in serum. The linear dependence of fluorescence intensity on NOR concentration, at a NOR to Al concentration ratio of 1:10, was found in the concentration range 0.001–2 μg/ml NOR with a detection limit of 0.1 ng/ml. The ability of aluminium (III) ion to form complexes with NOR was investigated by titrations in 0.1 M LiCl medium, using a glass electrode, at 298 K, in the concentration range: 2 × 10 −4 ≤ [ Al ] ≤ 8 × 10 −4 ; 5 × 10 −4 ≤ [ NOR ] ≤ 9 × 10 −4 mol/dm 3 ; 2.8 ≤ pH ≤ 8.3. The experimental data were explained by the following complexes and their respective stability constants, log ( β ± σ ): [ Al ( HNOR )], (14.60 ± 0.05); [Al(NOR)], (8.83 ± 0.08); [A1(OH) 3 (NOR)], (−14.9 ± 0.1), as well as several pure hydrolytic complexes of A1 3+ . The structure of the [Al(HNOR)] complex is discussed, with respect to its fluorescence properties.

Optimization of separation and determination of moxifloxacin and its related substances by RP-HPLC.

A RP-HPLC method for the separation and determination of impurities of moxifloxacin, in its pharmaceutical forms as well as moxifloxacin degradation products, was developed with the aid of DryLab software and chemometric (response surface) approach. The separation of four synthesis-related impurities was achieved on a Waters C(18) XTerra column using a mobile phase of (water+triethylamine (2%, v/v)): acetonitrile=90:10 (v/v%); the pH of water phase being adjusted with phosphoric acid to 6.0. Flow rate of the mobile phase was 1.5 ml/min and UV detection at 290 nm was employed. The column was thermostated at 45 degrees C. The resolution between the two least resolved impurity peaks was in average, R(s,min) > 1.5. Method validation parameters indicate linear dynamic range 0.2-2.0 microg/ml with LOQ ca. 0.20 microg/ml and LOD ca. 0.05 microg/ml for all analytes. The method was applied for the impurities determination in drug tablets and infusion (Avelox), Bayer AG) and for degradation products determination in a stability study of moxifloxacin. The impurity content in the tablets and infusion was quantified as 0.1% of total drug. Two degradation products were noted under hydrolytic conditions. The method can also be used for rapid and accurate quantification of moxifloxacin hydrochloride in its tablets during stability testing.

Spectrophotometry Determination of Ciprofloxacin in Serum Using Iron(III) Ion as Chromogenic Agent

ABSTRACT An analytical procedure for the determination of ciprofloxacin in serum without previous extraction has been developed. The determination was carried out using iron(III) nitrate as chromogenic agent, with the addition of sodium dodecylsulfate, at pH = 3.0. Absorbance was measured at 430 nm. The range of linearity was between 0.5 – 20.0 μg/mL with a detection limit 0.2 μg/mL.

Study of solution equilibria between aluminum(III) ion and ofloxacin.

The complex formation equilibria between aluminium(III) ion and ofloxacin in 0.1 mol/l(-1) ionic medium at 298 K were studied by glass electrode pH-metric and UV spectrophotometric measurements. Within ofloxacin to aluminium mole ratio ranging from 2:1 to 25:1 and in pH interval from 2.5 to 10.5, the obtained experimental results were explained by the formation of the following complexes: AI(Hoflo) (log beta1,1,1 = 15.93 +/- 0.03), Al(oflo)2 (log beta1,2,0= 14.84 +/- 0.07), Al(oflo) (log beta1,1,0 = 10.20 +/- 0.04) as well as several other mixed and pure hydrolytic complexes. The structure and mechanism of the formation of the complexes and their possible implications on aluminum toxicity were discussed.

Chemometric Optimization of a RP‐HPLC Method for the Simultaneous Analysis of Abacavir, Lamivudine, and Zidovudine in Tablets

Abstract A method has been developed and validated for the separation of abacavir, lamivudine, and zidovudine by high‐performance liquid chromatography (HPLC) on a C18 column with uv detection at 270 nm. The optimal conditions for separation were determined with the aid of a “critical resolution map” technique using the program DryLab®. The effect of simultaneously varying the pH and proportion of methanol in the mobile phase was studied to optimize the separation. A response surface diagram was used to study the interaction between factors determining the separation. The mobile phase composition that provides an optimal resolution of components in an acceptable elution time is water:methanol (60:40 v/v) + 0.2% TEA and pH = 3.20 (pH adjusted with H3PO4). A method is applied for the analysis of Trizivir® tablets (Glaxo Wellcome, UK). The powdered tablets were extracted with methanol:water (50:50 v/v) mixture and after addition of stavudine as an internal standard subjected to HPLC analysis and assayed by comparison of analyte to internal standard peak areas to concentration ratios.

High-performance liquid chromatographic assay of fleroxacin in human serum using fluorescence detection.

A HPLC method has been developed for the direct assay of fleroxacin in serum, without previous extraction. Serum samples, after the addition of sodium dodecylsulfate (0.5%), were injected directly into an LC Hisep column. The mobile phase consisted of acetonitrile, water and triethylamine in a per cent volume ratio 18:80:2. The pH of the mobile phase was adjusted to 6.50 with the addition of phosphoric acid. The drug was detected fluorometrically at lambda (ex )=280 nm and lambda (em )=450 nm . The linear concentration range of fleroxacin was between 0.01 and 2.0mg/l with a detection limit of 1ng/ml.

Fluorometric and derivative spectrophotometric determination of norfloxacin

Abstract The method for the direct determination of norfloxacin, without prior separation, in serum and pharmaceutical formulations, by means of fluorometry and second derivative u.v. spectrophotometry, was developed. Fluorometric assay of norfloxacin in serum was carried in 0.1 M HCl, with the adition of sodium-dodecylsulphate, at emission wavelength 450 nm (excitation 320 nm). Linear calibration curve was obtained in the concentration range 20 – 320 μg/L with the detection limit 2μg/L. The second derivative spectrophotometry was used for the determination of the norfloxacin in tablets at 337 nm using 0.05 M NaOH as solvent. Detection limit was 30μg/L.

Synthesis, cytotoxic activity and DNA-interaction studies of novel anthraquinone-thiosemicarbazones with tautomerizable methylene group.

A series of novel anthraquinone-thiosemicarbazone derivatives in a tautomerizable keto-imine form was synthesized and tested for their in vitro cytotoxic activity against human cancer cells (HeLa, MDA-MB-361, MDA-MB-453, K562, A549) and human normal MRC-5 cells. Several compounds efficiently inhibited cancer cell growth at micromolar concentrations, especially against K562 and HeLa cells. As determined by flow cytometric analysis, anthraquinone-thiosemicarbazone caused significant increase in the number of sub-G1 phase of HeLa cells and apoptosis in a concentration-dependent manner. Also, inhibition of caspase-3, -8, and -9 with specific caspase inhibitors reduced the apoptosis mediated by the tested compounds in HeLa cells. All anthraquinone-thiosemicarbazones exhibit calf thymus DNA-binding activity, but no cleavage of plasmid DNA was observed.

Study of solution equilibria between iron(III) ion and ciprofloxacin in pure nitrate ionic medium and micellar medium

Abstract Prototropic equilibria (protonation, hydrolytic and complexation) in iron(III) ion+ciprofloxacin (Hcipx) solutions were studied in 0.1 and 0.5 mol dm −3 (Na)NO 3 ionic media in the absence and in the presence of ionic surfactants: sodium dodecyl sulfate (SDS) or cetyltrimethylammonium bromide (CTAB). Experiments were carried out at 298±0.2 K using glass electrode potentiometric and UV–Vis spectrophotometric measurements. The concentration of SDS in Fe III –ciprofloxacin solutions was 10 mmol dm −3 while that of CTAB was 8 mmol dm −3 . The hydrolysis of the iron(III) ion was studied separately within the concentration range of iron 1–5 mmol dm −3 and pH 1.6–3.0. Non-linear least-squares treatment of the data indicates that in both ionic media studied the main hydrolytic products were Fe(OH) 2 + and Fe 2 (OH) 2 4+ . The effect of the concentration of the nitrate ion on the stability constants of these complexes is much more pronounced than the effect of the addition of either SDS or CTAB. The successive protonation constants of ciprofloxacin anion, cipx − , relating to the formation of Hcipx and H 2 cipx + species, were influenced to a significant extent by the presence of SDS and, to a considerably lesser extent, by the presence of CTAB in both studied concentrations of NO 3 − ionic media. The complexation between iron(III) and ciprofloxacin was studied in the concentration range of iron(III) 0.15–0.58 mmol dm −3 , with ligand to metal concentration ratios ranging from 3:1 to 10:1 in the pH interval 2.0–6.0. The experimental data obtained could be explained by the formation of mononuclear complexes: Fe(cipx) 2 + , Fe(cipx) 2+ and Fe(OH)cipx. In the presence of either SDS or CTAB the same complexes were formed; however, much higher formation constants were obtained with SDS, while the effect of CTAB was sluggish. The structure and mechanism of formation of iron(III)–ciprofloxacin complexes in pure ionic and in micellar media are discussed.

Preparation and molecular structure of the trans(O6) isomer of dihydrogen (1,3-propanediamine-N,N′-diacetato-N,N′-di-3-propionato)copper(II) complex. The stereochemistry of copper(II)-edta-type complexes in relation to the structure of the ligand

Abstract The hexadentate complex [Cu(H21,3-pddadp)] · 1.5H20 (1,3-pddadp = 1,3-propanediamine-N,N′-diacetate-N,N′-di-3-propionate ion) has been prepared and isolated and its molecular structure determined by the single crystal X-ray diffraction technique. The complex is a trans(O6) isomer, in which the copper(II) ion is surrounded octahedrally by two nitrogen and four oxygen atoms of 1,3-pddadp with two protonated β-alaninate rings in trans positions. The copper atom environment is a tetragonally elongated octahedron with tetragonality (T) 0.798. A comparison of structures of the copper(II)-edta-type complexes shows an expected variation in their stereochemistry, depending on the structure of the ligand. The 1,3-pddadp ligand encircles the CuII ion more favourably than the edta ligand, which is capable of forming five-membered chelate rings only. Some properties of the complex are also given.