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Biomedical subjects

Melissa Hanna-Brown

Publications and source records attributed to Melissa Hanna-Brown.

4 recordsLinked to original sources

Evaluation of multidimensional capillary electrophoretic methodologies for determination of amino bisphosphonate pharmaceuticals.

Alendronate and pamidronate are amino bisphosphonate analogues of pyrophosphate used for the treatment of a variety of bone diseases. Analysis of these compounds is problematic due to their polar ionic nature, lack of a suitable chromophore and chelation properties and current analytical approaches involve extensive sample preparation and derivatization procedures. The potential of multidimensional capillary electrophoretic methodological approaches, which eliminate sample preparation have been evaluated for the analysis of these compounds both in aqueous and urinary matrices. Capillary isotachophoresis (cITP) was employed as a pre-separation and on-line sample concentration step prior to analytical determination using either cITP or capillary zone electrophoresis (CZE) with conductivity detection. Single cITP, cITP-cITP and cITP-CZE approaches were partially validated with respect to repeatability, recovery and linearity of response for both compounds. The increases in sensitivity achievable through increasing injection volume from 30 to 300 microL may render such strategies appropriate for determination of these agents at biologically relevant concentrations with minimal sample work-up.

Alendronate↗

Toxicological classification of urine samples using pattern recognition techniques and capillary electrophoresis.

In toxicology, hazardous substances detected in organisms may often lead to different pathological conditions depending on the type of exposure and level of dosage; hence, further analysis on this can suggest the best cure. Urine profiling may serve the purpose because samples typically contain hundreds of compounds representing an effective metabolic fingerprint. This paper proposes a pattern recognition procedure for determining the type of cadmium dosage, acute or chronic, administrated to laboratory rats, where urinary profiles are detected using capillary electrophoresis. The procedure is based on the composition of a sample data matrix consisting of areas of common peaks, with appropriate pre-processing aimed at reducing the lack of reproducibility and enhancing the potential contribution of low-level metabolites in discrimination. The matrix is then used for pattern recognition including principal components analysis, cluster analysis, discriminant analysis and support vector machines. Attention is particularly focussed on the last of these techniques, because of its novelty and some attractive features such as its suitability to work with datasets that are small and/or have low samples/variable ratios. The type of cadmium administration is detected as a relevant feature that contributes to the structure of the sample matrix, and samples are classified according to the class membership, with discriminant analysis and support vector machines performing complementarily on a training and on a test set.

Animals↗

Micellar electrokinetic capillary chromatography and data alignment analysis: a new tool in urine profiling.

The complex nature of biofluids demands efficient, sensitive and high-resolution analytical methodologies to examine how the 'metabolic fingerprint' changes during disease. This paper describes how sulphated beta-cyclodextrin-modified micellar electrokinetic capillary chromatography (SbetaCD-MECC) has been combined with data alignment analysis and may prove a useful new tool in urine profiling, allowing for separation of over 80 urinary analytes in under 25 min. The optimised and validated SbetaCD-MECC methodology combined with data alignment analysis provides rapid identification of 'mismatches' between urine profiles which are not easily detected with the naked eye as well as a 'similarity score' which indicates the total sum of differences between one profile and another. The combination of SbetaCD-MECC with data alignment software should prove a useful alternative tool in metabonomic studies for rapid comparison of urine profiles.

Acetaminophen↗

Enantiomeric resolution of 2-arylpropionic acid nonsteroidal anti-inflammatory drugs by capillary electrophoresis: methods and applications.

The 2-arylpropionic acids (2-APAs) are an important group of nonsteroidal anti-inflammatory drugs. These agents, the majority of which are available as racemates, exhibit stereoselectivity in both their action and disposition. Developments in stereoselective separation science methodology, mainly chromatographic, have facilitated an evaluation of the pharmacological properties of the individual enantiomers of these drugs and contributed to our understanding of both their mode(s) of action and disposition. While a number of electrophoretic techniques, including capillary electrophoresis, capillary electrochromatography and isotachophoresis, have been applied to the stereoselective resolution and stereospecific analysis of these agents using a variety of chiral selectors, e.g., cyclodextrins, oligosaccharides, macrocyclic antibiotics, and proteins, the number of published applications in pharmaceutical and biomedical analysis remains relatively limited. However, the utility of electrophoretic techniques for stereospecific analysis may be illustrated using the 2-APAs as typical examples of chiral acidic pharmaceuticals. Applications include: determination of enantiomeric composition following biosynthetic stereoselective hydrolysis; examination of both achiral and chiral impurity profiles in bulk drugs and formulated products; determination of enantiomeric impurities in both bulk drugs and formulated products; examination of configurational stability following stress testing of formulated products; determination of enantiomeric composition and metabolite profile in biological fluids following administration of the racemates and individual enantiomers. It may be anticipated that future exploitation of electrophoretic approaches to the stereospecific analysis of these agents will result in further contributions to our understanding of their stereoselective biological properties and therapeutic use.

Anti-Bacterial Agents↗