Gianfranco Corbini

Nuclear relaxation studies in ligand-macromolecule affinity index determinations

Abstract An ‘affinity index’, representing the global affinity between a ligand and a biomacromolecular receptor, is proposed. It is determined as the slope of the linear relations between ΔR1SE and the receptor concentration and has the advantage of providing a measure of the ligand-biomacromolecule global affinity which is independent of the number of interaction sites. The method was applied to the calculation of the lamotrigine-albumin affinity index.

Determination of some quinolones in tablets, human plasma and urine by differential-pulse polarography

Abstract A differential pulse polarographic method was developed for the determination of norfloxacin, cinoxacin and pipemidic. oxolinic and piromidic acids in tablets and biological fluids. Well defined peaks, useful for an accurate and precise assay, were observed in the appropriate supporting electrolyte (Britton-Robinson and phosphate buffers), depending on both the kind of preparation (tablet, plasma or urine) and the quinolone investigated. The analysis of quinolones in biological fluids requires a prior clean-up procedure (treatment with acetonitrile and 2 M potassium hydroxide for plasma and solid-liquid extraction for urine) while common excipients were found not to interfere in the tablet assay. In each of the above situations (tablet, plasma or urine), good precision of the method evaluated as the CV, was found.

Drug analysis by near-infra-red reflectance spectroscopy. Determination of the active ingredient and water content in antibiotic powders

Near-infra-red reflectance spectroscopy is used to determine the active ingredient concentration and water content of an antibiotic powder (ceftazidime pentahydrate). The validity of predictive models for active ingredient concentrations and water content, constructed by means of the multiple linear regression technique is discussed. A procedure is devised for the analysis of production samples, which, on account of the very limited range of concentrations, prove a difficult fit to the above-mentioned model. The results obtained in testing formulation samples from 1 years industrial production are used to illustrate the potential of the technique.

Synthesis, spectroscopic and DFT structural characterization of two novel ruthenium(III) oxicam complexes. In vivo evaluation of anti-inflammatory and gastric damaging activities

The reactions of ruthenium(III) chloride trihydrate with piroxicam (H2PIR) and tenoxicam (H2TEN), two widely used non-steroidal anti-inflammatory drugs, afforded [Ru(III)Cl2(H2PIR)(HPIR)],·1, and [Ru(III)Cl2(H2TEN)(HTEN)],·2. Both compounds were obtained as pure green solids through purification via flash column chromatography. Characterizations were accomplished through UV-vis and IR spectroscopy, potentiometry and HPLC. Quantum mechanics and density functional computational methods were applied to investigate their respective molecular structures. The experimental and computational results are in agreement with a pseudo-octahedral coordination where the two chlorido ligands are in trans positions (apical) and the two trans-N,O chelating oxicam ligands occupy the equatorial sites. Both compounds revealed an acceptable solubility and stability profile upon dissolution in a standard buffer at physiological pH. Nonetheless, the addition of biologically occurring reducing agents caused spectral changes. The two complexes manifested a poor reactivity with the model proteins cytochrome c and lysozyme: no evidence for adduct formation was indeed obtained based on a standard ESI MS analysis; in contrast, some significant reactivity with serum albumin was proved spectrophotometrically. Remarkably, both study compounds revealed pronounced anti-edema effects in vivo suggesting that the pharmacological actions of the ligands are mostly retained; in addition, they were less irritating than piroxicam on the gastric mucosa when the coordination compounds and free oxicam were administered at the same overall molar concentration of the ligand. Overall, the present results point out that ruthenium coordination may represent an effective strategy to improve the pharmacological properties of oxicam drugs reducing their undesired side effects.

Polarographic determination of total pyrethroid residues in stored cereals

A new method for determination of the total cyanopyrethroid residue concentration in stored cereals by differential-pulse polarography is proposed. Cyanopyrethroids were previously extracted with a non-polar solvent and purified by solid-phase extraction. The total pyrethroid residue concentrations are determined by differential-pulse polarography of 3-phenoxybenzaldehyde formed quantitatively by rapid and reproducible alkaline alcoholysis of the sample. The method is linear, quantitative and reproducible for maize and wheat analysis in the range 0.1–3.0 mg kg–1. A thin-layer chromatographic method for identification of six widely used cyanopyrethroids in the sample is described. The electrodic reduction process of 3-phenoxybenzaldehyde is examined and the reduction products isolated and identified.

Quantification of psychosine in the serum of twitcher mouse by LC-ESI-tandem-MS analysis.

Globoid cell leukodystrophy or Krabbe disease is an inherited autosomal recessive disorder caused by mutations in the galactosylceramidase (GALC) gene. Deficiency of GALC results in the accumulation of a highly cytotoxic metabolite galactosylsphingosine (psychosine). In the present study, we describe the development and validation of a sensitive and specific LC-ESI-tandem-MS method for the determination of psychosine in the serum of twitcher mice, the naturally occurring animal model of this disease. The method was validated in terms of accuracy, precision, specificity, linearity and sensitivity. Calibration plots were linear over the concentration range of 2.5-50ng/mL. Recovery of psychosine from serum was in the range 94.20-98.02%. The results of this study show that in the affected mice the concentration of psychosine (ranging from 2.53 to 33.27ng/mL) increased significantly with the progression of the disease. The maximum level (33.27ng/mL) was detected in the serum of one of the twitcher mice sacrificed at 40PND. Psychosine was not detected at significant levels in wild type mice. These results clearly demonstrate that this noninvasive, rapid, and highly sensitive LC-ESI-tandem-MS method is a very useful approach for the detection of psychosine in serum.

SPECTROSCOPIC INVESTIGATION OF THE CONFORMATIONAL PROPERTIES AND SELF-ASSOCIATION BEHAVIOR OF NATURAL COMPOUNDS IN SOLUTION

ABSTRACT The conformational properties and self-association behaviour of rifaximin and rifaximin OR (Open Ring) were investigated in solution by NMR and IR spectroscopy. The dependence of proton chemical shift on concentration and temperature were analysed to study the self-association process. IR spectra of rifaximin and rifaximin OR were also used at different concentrations to investigate the entity of specific inter- and intra-molecular interactions. Although similar in structure the two molecules had different chemical properties in solution. This could be of some interest in view of the biological importance of this class of antibiotic molecules.

Thin-layer chromatography and densitometry in drug assay: Comparison of methods for monitoring valproic acid in plasma

A thin-layer chromatographic (TLC) method is described for the assay of the anti-epileptic drug, valproic acid, in plasma. The use of high-performance (HPTLC) plates gave sensitive detection limits (4.87 micrograms ml-1) for derivatives of valproic acid and the reproducibility on the same or different plates was good. Comparison with high-performance liquid chromatography showed a similar performance of plate and column.

Application of NIR Reflectance Spectroscopy to the Identification of Drugs Derived from Plants

AbstractNIR reflectance spectroscopy was applied to the identification of plant drugs. It was possible to satisfactorily distinguish ginseng, Silybwn marianum and grape seeds, directly analysing the product in its finished form. It was possible to identify Silybum samples grown in different areas. Ginseng samples containing starch were identified and old and young roots were distinguishable. Semiquantitative assay of ginsenoside content was possible.

Determination of diisocyanate monomers in air by differential-pulse polarography

A method for the determination of hexane-1,6-diyl diisocyanate, 1-isocyanato-3-isocyanatomethyl-3,5,5-trimethylcyclohexane, toluene-2,4-diyl diisocyanate and toluene-2,6-diyl diisocyanate in air by differential-pulse polarography (DPP) is described. The monomers are derivatized with 4-nitro-N-propylbenzylamine (nitro reagent). The excess of nitro reagent is removed by using solid-phase extraction columns and the ureido derivatives are determined by DPP in 0.2 mol dm–3 KOH [methanol–water (80 + 20)] as the total concentration of diisocyanate in the sample.