Determination of cyclosporine A in whole blood: comparison of a chromatographic method with three different immunological methods

Cyclosporine A is potent immunosuppressive agent characterized by a narrow therapeutic range, inter- and intra-individual variability and a lack of correlation between drug dosage and blood levels. In view of these facts, blood levels of CyA should be routinely monitored to assess organ rejection and toxicity.

We evaluated CyA as well as its metabolites (AM9, AM19, AMl, and AM4N) in whole blood samples from 117 patients using commercially available immunological assays (AxSYM, EMIT, Dimension) and HPLC.

Cross-reactivity of the immunological assays was evaluated using different concentrations of the CyA metabolites (in vitro cross-reactivity) and by statistical analysis of patient data (in vivo cross-reactivity). Cross-reactivity was seen in all immunological assays, with differences in in vitro and in vivo cross-reactivity.

The statistical analysis showed a classical correlation between HPLC and AxSYM of r² = 0.89, HPLC versus EMIT of r² = 0.93, and HPLC versus Dimension of r² = 0.93.

The percentage metabolite cross-reactivity (%) by immunological assays for four metabolites at two concentrations each (250 and 1000 ng ml⁻¹) was lowest with the Dimension assay.

Of the immunological methods examined, the new Dimension for CyA determination can be relied on to produce results comparable to HPLC; other advantages are its simplicity, practicability and ease of handling.     

Ferrocene-modified pyrimidine nucleosides: synthesis, structure and electrochemistry

This paper reports syntheses, crystal structures and electrochemical results for two ferrocene(Fc)-modified pyrimidine nucleosides that could potentially be used for investigating electron transfer in DNA. Fc was directly attached to the 5-position of deoxyuridine and deoxycytidine via the Stille coupling reaction. Fc-modified uridine was incorporated into DNA trinucleotides with standard solid-phase synthesis. The structures of corresponding detritylated compounds were determined by single-crystal X-ray analysis. Electrochemical investigations of all compounds by cyclic voltammetry revealed reversible redox processes.     

Determination of total dissolved inorganic carbon in freshwaters by reagent-free ion chromatography

Studies of inorganic carbon cycle in natural waters provide important information on the biological productivity and buffer capacity. Determination of total inorganic carbon, alkalinity and dissolved carbon dioxide gives an indication of the balance between photosynthesis and respiration by biota, both within the water column and sediments, and carbon dioxide transfers from the water column to the atmosphere. There are few methods to measure and distinguish the different forms of inorganic carbon, but all require a measure or an indirect quantification of total inorganic carbon. A direct measurement of TIC in water is made possible by the introduction of electrolytic generated hydroxide eluent in ion chromatography which allows to detect a chromatographic peak for carbonate. The advantage of this method is that all the inorganic forms of carbon are converted in carbonate at eluent pH and can be detected as a single peak by conductivity detection. Repeatability of carbonate peak was evaluated at different levels from 0.02 to 6 mequiv.l(-1) both in high purity water and in real samples and ranged from 1 to 9%. The calibration curve was not linear and has to be fitted by a quadratic curve. Limit of detection was estimated to be 0.02 mequiv.l(-1). Accuracy has been estimated by comparing ion chromatography method with total inorganic carbon calculated from alkalinity and pH. The correlation between the two methods was good (R(2)=0.978, n=141). The IC method has been applied to different typologies of surface waters (alpine and subalpine lakes and rivers) characterised by different chemical characteristics (alkalinity from 0.05 to 2 mequiv.l(-1) and pH from 6.7 to 8.5) and low total organic carbon concentrations. This analytical method allowed to describe the distribution of TIC along the water column of two Italian deep lakes.     

Synthesis and crystal structure of bis(2-methylbenzimidazolium) tetrahalocuprate(II)

The crystal structures of 2-methylbenzimidazolium tetrahalocuprates (H2-mebz)₂[CuX₄] (X = Cl and Br) have been detemined. The chloride salt is monoclinic, P2₁/c, with a = 8.540(2) Å, b = 16.591(2) Å, c = 14.303(3) Å, and = 98.69(2)°. The bromide salt is also monoclinic, P2₁/c, with a = 8.316(3) Å, b = 17.436(3) Å, c = 14.747(3) Å, and = 98.82(3)°. Both the compounds contain discrete distorted tetrahedral CuX₄ ^2– anions and almost planar 2-methylbenzimidazolium cations. In the chloride salt, three chloride ions are involved in hydrogen bonding instead of two bromide ions in the bromide salt.     

Synthesis of enantiomerically enriched amino sulfide building blocks from acyclic chiral amino allylsilanes

An efficient synthesis of various protected syn-β-sulfenyl amides is described. These are prepared from the corresponding enantiopure amino allylsilanes which are in turn obtained from naturally occurring amino acids. The key step for introduction of the sulfur substituent is a diastereoselective electrophilic sulfodesilylation which is carried out with phthalimidesulfenyl chloride. The resulting homochiral β-phthalimidesulfenyl amines with an allylic sulforated stereogenic center are useful building blocks, as they represent a starting point for subsequent functional manipulations.     

Photodissociation dynamics of chlorine peroxide adsorbed on ice

Chlorine peroxide plays an important role in the chlorine-ozone chemistry in the antarctic stratosphere. Adsorption by ice crystals may alter its photochemistry in different ways. We have simulated the photodissociation of a ClOOCl molecule adsorbed on ice by means of a semiclassical representation of the excited state dynamics. Electronic energies and wave functions of ClOOCl are computed by an ad hoc reparametrized semiempirical method, and the interaction with ice is taken into account by a QM/MM strategy. The reaction mechanism is similar to what was previously found for the isolated molecule: sequential or almost simultaneous breaking of both Cl-O bonds leads to the 2Cl + O2 reaction products in most cases. The Cl atoms remain temporarily adsorbed on the ice surface, whereas O2 is ejected. The main effect for the overall chlorine chemistry is probably an increase of the photodissociation rates at long wavelengths, due to the change of adsorption cross sections induced by the interaction with ice.     

Structural and thermal characterization of L‐arginine dihydrate ‐ a nonlinear optical material

Crystal structure and thermal stability of the hydrated crystals of the basic amino acid L‐arginine named as L‐arginine dihydrate (LAD), a nonlinear optical material have been reported here. The title compound crystallized in the space group P2₁2₁2₁ with Z=4 and unit cell dimensions a=11.856(2)Å, b=15.694(2)Å, c=5.664(3)Å. The arginine molecule is a zwitterion with the guanidyl group accepting an extra proton from the carboxylate group. DTA‐TG analysis gives an idea about the thermal behaviour of LAD and ruled out the possibility of structural changes independent of mass changes. © 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim