HPLC determination of pyroglutamic acid as a degradation product in parenteral amino acid formulations

Summary The aminoacid glutamine in aqueous solution and in conditions of high temperature and long term storage is partly transformed into pyroglutamic acid which exhibits potential neurotoxic effects.Commercially available aminoacid mixtures supplemented with glutamine are heat-sterilized and some losses of glutamine and formation of pyroglutamic acid may occur.The aim of the work was to set up an easy and reliable HPLC method which allows the determination of pyroglutamic acid as a degradation product of glutamine. The column was a 5 m Hypersil ODS (100×4.6 mm) and the mobile phase 100% 0.007 M phosphate buffer pH 3.5.Stability studies in different conditions of temperature and time of storage were performed on aminoacid mixture available in the commerce.     

Search of ligands for the amyloidogenic protein beta2-microglobulin by capillary electrophoresis and other techniques

Beta2-microglobulin (beta2-m) is a small amyloidogenic protein normally present on the surface of most nucleated cells and responsible for dialysis-related amyloidosis, which represents a severe complication of long-term hemodialysis. A therapeutic approach for this amyloidosis could be based on the stabilization of beta2-m through the binding to a small molecule, and consequent inhibition of protein misfolding and amyloid fibril formation. A few compounds have been described to weakly bind beta2-m, including the drug suramin. The lack of a binding site for nonpolypeptidic ligands on the beta2-m structure makes it difficult for both the identification of functional groups responsible for the binding and the search of hits to be optimized. The characterization of the binding properties of suramin for beta2-m by using three different techniques (surface plasmon resonance, affinity CE (ACE), ultrafiltration) is here described and the results obtained are compared. The common features of the chemical structures of the compounds known to bind the protein led us to select 200 sulfonated/suramin-like molecules from a wider chemical library on the basis of similarity rules, so as to possibly single out some interesting hits and to gain more information on the functional groups involved in the binding. The development of screening methods to test the compounds by using ultrafiltration and ACE is described.     

HPLC determination of urinary 2,4- and 2,6-toluendiamines as potential degradation products of polyurethane breast implants

Summary A reversed-phase HPLC method has been developed for the urinary determination of mutagenic 2,4- and 2,6-toluendiamines. These amines are degradation products of polyurethane, a material used to cover textured silicone breast implants. FMOC-Cl was used as fluorescent derivatising agent in order to obtain a limit of detection of 15 ng/ml in urine. Pre-treatment of urine samples was by liquid/liquid extraction and urine specimens of patients after surgury were analysed.     

An inverse problem in potential theory

Summary We consider the classical problem of finding the density of a material body embedded into a region S, when the potential generated by (possibly coinciding with S) is known outside (or on the surface of) S. In the set of such solutions we look for the density which has the smallestL ²-norm and we prove that belongs toL _H ²⁼ (), the space of square summable functions harmonic in . However is unstable, i.e. itsL ²-norm does not depend continuously upon the L₂-norm of the potential. We show how a continuous dependence may be restored by introducing mild restrictions on the set of admissible solutions.     

‐Theory for Schrödinger systems

In this article, we study for the ‐realization of the vector‐valued Schrödinger operator . Using a noncommutative version of the Dore–Venni theorem due to Monniaux and Prüss, we prove that the ‐realization of , defined on the intersection of the natural domains of the differential and multiplication operators which form , generates a strongly continuous contraction semigroup on . We also study additional properties of the semigroup such as extension to L¹, positivity, ultracontractivity and prove that the generator has compact resolvent.     

On elliptic equations with piecewise constant coefficients

In this work we prove an existence and uniqueness theorem for solutions in ²(R^t) of second order elliptic equations with coefficients that are constant on the half-spaces R+ⁿ and R ?ⁿ     

Linear First-Order Evolution Problems Without Initial Conditions

Direct and inverse problems for first-order in time linear evolution problems without initial conditions, i.e. related to the unbounded time-intervals (−∞, 0] and \mathbbR{\mathbb{R}}, are considered in the framework of Banach spaces. Some degenerate in time problems related to a bounded time-interval are also considered. The approach for solving the previous problems is related to both C ₀-and Analytic Semigroup Theory.     

On the Conformation of a Sterically Congested Amide Group in the Crystalline State and in Solution

The conformation in the crystalline state and in solution of the sterically congested tetramethylpiperidinederived amide group of the symmetric diamide I formed from 2,2,6,6-tetramethylpiperidine ( b ) and 1,2,5-thiadiazole-3,4-dicarbonyl dichloride ( c ), and of the mixed diamide II derived from b , c , and piperidine ( a ) has been investigated. In crystals, as observed with II , this group is strongly bent out-of-plane at both the N-atom and the carbonyl C-atom, and there is also a sizable twisting around the amide bond. Furthermore, the amide bond is abnormally long (1.37 Å). In CD₂Cl₂ (or CDCl₃) solution, the group is apparently planar in its ground-state conformation, but the energy barrier to rotation around the amide bond is low. This conclusion is based on low-temperature ¹H-NMR measurements on I , II , and on the symmetric diamide III derived from a and c .