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Biomedical subjects

A F Fell

Publications and source records attributed to A F Fell.

11 recordsLinked to original sources

Evaluation of the anti-tumour action and acute toxicity of kosins from Hagenia abyssinica.

The kosins are phloroglucinol derivatives isolated from female flowers of Hagenia abyssinica (Rosaceae) and were tested for possible cytotoxic activity in vitro and in vivo against a panel of three transplantable murine adenocarcinomas of the colon of varying growth characteristics and morphology (MAC system). Significant reductions in colony formation were observed in vitro in MAC 15A tumour following 1, 3, 6 and 24 h exposure to all kosins (alpha-kosin, kosotoxin and protokosin). The kosins (kosotoxin and protokosin) were also found to be cytotoxic against MAC tumour cells in vivo in some cases. Kosotoxin was subjected to preliminary toxicity studies in mice. It showed no observable toxicity up to 200 mg kg-1 orally and was found to be toxic at doses in excess of 50 mg kg-1 (i.p.). A single dose of 100 mg kg-1 (i.p.) was lethal for 100% of the animals.

Administration, Oral

A multiwavelength approach to the selection of absorbance ratios for the assessment of chromatographic peak purity.

The routine use of diode-array detectors (DAD), based on the linear photodiode array device, has transformed the practice of UV-vis detection in liquid chromatography (LC). Multiwavelength detection is widely employed to generate absorbance ratios as a relatively non-specific method for characterizing peak purity in LC. If several wavelength pairs are selected the selectivity of the absorbance ratio method and its sensitivity to an interfering impurity can be increased, however, these attributes still depend on the selection of suitable pairs of wavelengths. This paper presents a novel approach to the selection of absorbance ratios for the assessment of peak purity in LC, utilizing a matrix derived from all the spectral data collected. As with single absorbance ratios, the absorbance ratio matrix (ARM) generated (containing all possible finite absorbance ratios) is characteristic for the analyte and independent of the analyte concentration. Moreover, the ARM technique eliminates the need to select "appropriate wavelength pairs", for sensitive discrimination of small spectral differences, when used for peak purity assessment. The ARM is found to give comparably high sensitivity to the presence of co-eluting species, as compared with the use of the wavelength pair selected on the basis of the conventional optimization criteria.

Chemistry Techniques, Analytical

Chromatographic and spectroscopic analysis of bound and unbound phenolic acids in Lagenaria breviflora fruit.

The fruit pulp of Lagenaria breviflora Robert (Cucurbitaceae), used in Nigeria as an anti-bacterial and anti-fertility drug, was found to contain phenolic acids. Isolation and characterization of these compounds was based on column chromatography, TLC, PC, UV, IR and GC-MS. While p-hydroxybenzoic and vanillic acids were found to occur as free and bound acids in the pulp, ferulic acid was found to occur only as an ester. An optimized HPLC procedure for the quantitative analysis of these acids was developed, featuring short retention, times, high sensitivity and excellent resolution. The concentration of these phenols in the fruit mesocarp was established.

Chromatography, High Pressure Liquid

Diode array detection and simultaneous quantitation of the coeluting atenolol-related synthetic route impurities, PPA-Diol.

The diode array multichannel detector is used to acquire spectral information at specified intervals in the elution profile of atenolol and its related impurities for post-chromatographic data analysis. The applicability of a number of peak homogeneity testing methods, including spectral normalization, absorbance ratio, chromatographic derivatives, and spectral suppression (SS), are assessed for suitability in simultaneous determinations of the coeluting atenolol-related synthetic impurities, PPA-Diol. Spectral suppression displays a superior performance in comparison to all the other techniques in that both qualitative and quantitative information are acquired on the system.

Acetamides

Assessment of chromatographic peak purity of drugs by multivariate analysis of diode-array and mass spectrometric data.

Numerous multivariate chemometric approaches have been developed for LC-UV data acquired using a diode-array detector (DAD), but these methods have not been widely exploited for LC-MS data. Principal component analysis (PCA) and subsequent axis rotation within the reduced factor space are assessed for LC-DAD and LC-MS data as approaches for estimating the number of components (i.e. the rank of the data) under a single chromatographic peak for compounds whose UV-spectra are very similar. Multivariate techniques for LC-DAD data are shown to suffer from inherent limitations of sensitivity for the minor components. The novel technique in LC-MS of plotting the rotated PCA data in two-dimensional factor space generates characteristic ion clusters, giving a visual criterion of peak purity. Single ion chromatograms produced subsequently confirm the profile of each coeluting component and give evidence of the degree of peak overlap. The application of this new chemometric technique to the detection of low levels of coeluting impurities by LC-MS is discussed as a novel approach for the validation of LC separations in pharmaceutical research and development.

Chromatography, Liquid

Design of chiral LC separations for calcium antagonists on alpha 1-acid glycoprotein and ovomucoid columns.

Three chiral calcium antagonist drugs, gallopamil and two dihydropyridine derivatives, have been successfully separated within short retention times using both the alpha 1-acid glycoprotein chiral stationary phase (Chiral-AGP) and the ovomucoid column (Ultron ES-OVM). Aqueous buffer at defined pH is modified by the addition of an organic component, in order to modulate the retention properties of each system. Optimization of pH and organic modifier is carried out using the modified simplex method, with Kaiser's peak separation function as a criterion. The influence of pH and percentage of organic modifier on retention, selectivity, resolution and column performance are discussed for the two dihydropyridines analysed on Chiral-AGP and Ultron ES-OVM stationary phases. A new method is proposed as a new chiral system suitability test for these protein-based phases, utilizing a racemic mixture of closely eluting verapamil enantiomers as a probe.

Calcium Channel Blockers