Development of a LC method for pharmaceutical quality control of the antimetastatic ruthenium complex NAMI-A.

Imidazolium trans-tetrachloro(dimethylsulfoxide)imidazoleruthenium(III) (NAMI-A) is a novel ruthenium complex with selective activity against metastases currently in Phase I clinical trials in the Netherlands. Pharmaceutical quality control of NAMI-A drug substance and lyophilized product warranted the development of an assay for determination and quantification of NAMI-A and degradation products. A high performance liquid chromatography (HPLC) method was developed, consisting of a C18 column with 0.

Pharmaceutical development of a parenteral lyophilized formulation of the antimetastatic ruthenium complex NAMI-A.

This paper describes the development of a stable pharmaceutical dosage form for NAMI-A, a novel antimetastatic ruthenium complex, for Phase I testing. NAMI-A drug substance was characterized using several spectrometric and chromatographic techniques. In preformulation studies, it was found that NAMI-A in aqueous solution was not stable enough to allow sterilization by moist heat.

A kinetic study of the chemical stability of the antimetastatic ruthenium complex NAMI-A.

NAMI-A is a novel ruthenium complex with selective activity against cancer metastases currently in Phase I clinical trials in The Netherlands. The chemical stability of this new agent was investigated utilizing a stability-indicating reversed-phase high performance liquid chromatographic assay with ultraviolet detection and ultraviolet/visible light spectrophotometry. The degradation kinetics of NAMI-A were studied as a function of pH, buffer composition, and temperature.

Structural characterization and solution properties of an acidic branched (1-->3)-beta-D-glucan from Aureobasidium pullulans.

An acidic exopolysaccharide was isolated from a selected strain of Aureobasidium pullulans. On the basis of spectroscopic and chromatographic techniques, the polymer was identified as a beta-D-glucan containing a main chain of (1-->3)-linked beta-D-glucopy-ranosyl units substituted at the O-6 position by single beta-D-glucopyranosyl side chains. The ratio of units in the main chain to units in the side chain was found to be 1.

Solution properties of the capsular polysaccharide produced by Klebsiella pneumoniae K40.

This paper reports some physicochemical properties of the capsular polysaccharide produced by Klebsiella pneumoniae serotype K40 (K40-CPS) in aqueous solution. The polymer has a linear hexasaccharide repeating unit containing one glucuronic acid residue as the only ionizable group. Potentiometric, viscometric, chiro-optical and rheological measurements have been carried out over a range of ionic strength, pH and temperature, with the aim of characterizing the conformational state of the polysaccharide in aqueous solution.

Solution properties of the capsular polysaccharide produced by Klebsiella pneumoniae SK1.

The solution properties of the capsular polysaccharide produced by Klebsiella pneumoniae SK1, SK1-CPS, were investigated by various methods. The SK1-CPS repeating unit is a branched pentasaccharide containing one glucuronic acid as single unit side chain; acetyl groups are present as non-carbohydrate substituents on the uronic acid residue in non-stoichiometric amounts. Chiro-optical, potentiometric, viscometric and rheological measurements have been performed in order to characterize the conformational behaviour of the polymer in water and in aqueous salt solutions.

NMR studies of oligosaccharides derived from hyaluronate: complete assignment of 1H and 13C NMR spectra of aqueous di- and tetra-saccharides, and comparison of chemical shifts for oligosaccharides of increasing degree of polymerisation.

A series of oligosaccharides was prepared from hyaluronate by depolymerisation with bovine testicular hyaluronidase. Complete assignment of the 1H and 13C NMR spectra was obtained for the disaccharide, the tetrasaccharide, and the NaBH4-treated tetrasaccharide, by using various 1D and 2D NMR methods. The 1H assignments for the tetrasaccharide differ from the incomplete data reported recently (ref.

Hyaluronan can be protected from free-radical depolymerisation by 2,6-diisopropylphenol, a novel radical scavenger.

The scavenging effect of 2,6-diisopropylphenol on hydroxy radicals produced by xanthine oxidase was assessed by evaluating the in vitro depolymerisation of hyaluronan in artificial synovial fluid by size-exclusion chromatography. After 1 hour, the number-average molecular weight of hyaluronan remained unchanged (100%) with 2,6-diisopropylphenol, whereas it dropped to 90% with methylprednisolone added, to 55% with the antioxidant 2,6-tert-butyl-4-methylphenol added, and to 10% of its initial value in the absence of scavenger.

Purification and characterization of hyaluronan from synovial fluid.

An easy and rapid method for the purification and characterization of hyaluronan from synovial fluid has been developed. Lipids were removed by filtration through a hydrophobic filter prior to the removal of proteins by phenol-chloroform extraction. The hyaluronan recovery was 95%, as measured by three different methods.