PubMed Health⌕ Search

Biomedical subjects

M W Coleman

Publications and source records attributed to M W Coleman.

8 recordsLinked to original sources
PubMed2003

Mathematical representation of electrophoretic mobility of basic drugs in ternary solvent buffers in capillary zone electrophoresis.

The electrophoretic mobilities of two beta-blocker drugs, i.e., labetalol and atenolol, have been determined in a mixed solvent background electrolyte system containing sodium acetate+acetic acid as buffering agent and different volume fractions of water, methanol and ethanol using capillary electrophoresis. The produced data and three other sets collected from a recent work are employed to study the accuracy and prediction capability of a mathematical model to calculate the electrophoretic mobility with respect to the volume fractions of the solvents in the mixture. The results show that the proposed model is able to correlate/predict the mobility within an acceptable error range and it is possible to use the model in industry to achieve the optimum solvent composition for the buffer where using a ternary solvent system is required. The average percentage deviations (APDs) obtained for correlated and predicted data points are 0.71-2.48 and 1.72-4.39%, respectively. The accuracy of the proposed model is compared with that of a mixture response surface method and the results show that the proposed model is superior from both correlation and prediction points of view. The possibility of calculation of the mobility of chemically related drugs in water-methanol-ethanol mixtures using the proposed model is also shown and the produced prediction APD is approximately 8%.

Electrophoresis, Capillary↗
PubMed2002

Calculation of electrophoretic mobility in mixed solvent buffers in capillary zone electrophoresis using a mixture response surface method.

The electrophoretic mobilities of three beta-blocker drugs, practolol, timolol and propranolol, have been measured in electrolyte systems with mixed binary and ternary water-methanol-ethanol solvents with acetic acid/sodium acetate as buffer using capillary electrophoresis. The highest mobilities for the analytes studied have been observed in pure aqueous, the lowest values in ethanolic buffers. The measured electrophoretic mobilities have been used to evaluate the accuracy of a mathematical model based on a mixture response surface method that expresses the mobility as a function of the solvent composition. Mean percentage error (MPE) has been computed considering experimental and calculated mobilities as an accuracy criterion. The obtained MPE for practolol, timolol and propranolol in the binary mixtures are between 0.9 and 2.6%, in the ternary water-methanol-ethanol solvent system the MPE was about 2.7%. The MPE values resulting from the proposed equation lie within the experimental relative standard deviation values and can be considered as an acceptable error.

Adrenergic beta-Antagonists↗
PubMed1999

Separation of the voriconazole stereoisomers by capillary electrophoresis and liquid chromatography.

A chiral capillary electrophoresis (CE) method has been developed for the direct separation of the four stereoisomers of a new broad spectrum antifungal agent, voriconazole. Cyclodextrin (CD) modified micellar electrokinetic chromatography employing, alpha-CD, beta-CD, gamma-CD, hydroxypropyl-beta-CD and hydroxyethyl-beta-CD was not sufficiently selective for the four neutral stereoisomers. Three anionic sulphobutyl-ether-beta-CD (SBE-beta-CD) electrolyte additives, each having a defined degree of substitution (DS) (6.5, 4.5 and 1.0) were subsequently examined. The complete CE separation of all four stereoisomers was obtained when using the medium substituted additive DS = 4.5. In liquid chromatography (LC), two approaches were examined for the direct chiral separation of the stereoisomers of voriconazole: (a) use of the neutral and anionic CD mobile phase additives and (b) a vancomycin chiral stationary phase. The CD additives were shown to be extremely selective for two stereoisomers of voriconazole (active drug and its enantiomer) but unable to discriminate between the opposite two stereoisomers. The converse was observed, however, when the vancomycin chiral stationary phase was employed.

Antifungal Agents↗
PubMed1997

Chiral recognition in liquid chromatography utilising chargeable cyclodextrins for resolution of doxazosin enantiomers.

The chromatographic resolution of rac-doxazosin using reversed-phase high performance liquid chromatography (HPLC) with the chargeable chiral mobile phase additive, carboxymethyl-beta-cyclodextrin (CM-beta-CD), is described. The effects of different modifiers (acetonitrile, methanol and tetrahydrofuran), pH, temperature, and cyclodextrin concentration were investigated to a) assess the key chromatographic parameters for subsequent chemometric optimisation, and b) explore the enantioselective mechanism. Assuming a 1:1 complex between each doxazosin enantiomer and CM-beta-CD, studies of the relationship between the capacity factors (k') and functions of CM-beta-CD concentration indicate that the mechanisms for retention and chiral selectivity are comparable with those proposed earlier by Sybilska et al. Stability constants (KG) calculated for rac-doxazosin complexed with CM-beta-CD (647 +/- 55 and 594 +/- 45 M-1 for each enantiomer respectively) are significantly larger than those calculated for the barbiturates complexed with beta-CD (ca. 101-108 M-1). Investigations on pH indicate an ionic or ino-pair interaction between the anionic CM-beta-CD and the cationic doxazosin enantiomers. A central composite design was used to optimise the key chromatographic parameters: pH, methanol (v/v) and CM-beta-CD concentration. The Kaiser peak separation index, Pi, was used for the response function. The predicted response for this chiral separation has been compared with that observed experimentally and samples of the four-dimensional response surface have been assessed for their value in showing robustness.

Adrenergic alpha-Antagonists↗
PubMed1997

Use of 1H-NMR spectroscopy to determine the enantioselective mechanism of neutral and anionic cyclodextrins in capillary electrophoresis.

One-dimensional (ID) and two-dimensional (2D) 1H nuclear magnetic resonance (NMR) techniques have been used to investigate the chiral recognition process in capillary electrophoresis (CE) for seven different cyclodextrins (CDs) with the calcium channel blocker amlodipine as a model compound. These include five neutral CDs (alpha-CD, beta-CD, gamma-CD, hydroxypropyl-beta-CD and hydroxyethyl-beta-CD) and two anionic CDs (sulphobutyl-ether-beta-CD and carboxymethyl-beta-CD) where mixtures of amlodipine with each of the seven CDs were examined by 1D NMR in deuterated phosphate buffer at pD 3.4. The resonance shift of signals with added CD, relative to the CD-free position (shift displacement, delta delta) and shift non-equivalence (delta delta *) of enantiomeric signals shifted relative to each other after addition of CD were examined for non-overlapped protons of amlodipine. The possible correlations of NMR shift non-equivalence data with chiral separation in CE for amlodipine have been critically assessed. Qualitative differences in the 1D NMR shifts and enhanced enantioselectivity in CE were observed for amlodipine with sulphobutyl-ether-beta-CD. Further experiments on the through-space interactions using 2D rotating frame nuclear Overhauser effect spectroscopy (ROESY) indicated that there was no association between internal glucopyranose hydrogen atoms and the aromatic hydrogens of amlodipine. This gives evidence for the aromatic ring not being included in this CD. Moreover, data from spin-lattice relaxation times (T1) measured for amlodipine in the free state and after addition of the anionic sulphobutyl-ether-beta-CD indicate that the aromatic moiety of amlodipine is not included into the sulphobutyl-ether-beta-CD cavity. There is evidence that it interacts with the sulphobutyl side chains, and may adopt a preferred orientation outside the sulphobutyl-ether-beta-CD toroid itself.

Amlodipine↗
PubMed1996

Method development in liquid chromatography with a charged cyclodextrin additive for chiral resolution of rac-amlodipine utilising a central composite design.

A negatively charged derivative of beta-cyclodextrin, sulphobutyl ether-beta-cyclodextrin (SBE-beta-CD), was examined as a chiral mobile phase additive in reversed-phase high-performance liquid chromatography for the enantiomeric resolution of the calcium channel blocker rac-amlodipine. Theoretical and practical aspects are discussed for setting up a central composite design applicable to any analytical method. These include the correct location of factor points for maintaining orthogonality within the design and the augmentation of centrepoint experiments to allow a larger factor space by increasing the distance of axial star points. Optimised separation was achieved using a reverse-phase column with eluent comprising: acetonitrile (ACN)-potassium dihydrogen phosphate (pH 3.93) containing 2.66 mM SBE-beta-CD (26.5:73.5% v/v) at a flow rate of 1.0 ml/min. This yielded a Kaiser peak separation index, Pi = 0.96, at tR2 = 52 min with satisfactory reproducibility, relative standard deviation values: tR1, 0.39%; tR2, 0.47% (n = 5). These experimental results were in excellent agreement with those predicted by the SAS software package for a chromatographic response function model. Multiple regression analysis in four dimensions, with three response models based on Rs, Pi, and a function of Pi, produced response surfaces which revealed zones of optimum robustness and illustrated the interactions involved between the key chromatographic factors. Putative proposals for a mechanism involving the interaction of each of the positively charged enantiomers with the negatively charged cyclodextrin are also discussed. These examine the possibility of ion-pairing and inclusion phenomena to account for the excellent resolution observed.

Amlodipine↗
PubMed1979

13C-NMR studies on 1-N-[(S)-4-amino-2-hydroxybutyl]kanamycin A (butikacin) and related aminoglycosides.

The 13C-NMR spectra of 1-N-[(S)-4-amino-2-hydroxybutyl]kanamycin A (butikacin) (Fig. 1, 1b) and some of its related compounds have been recorded and are tabulated, assigned and discussed. The chemical shifts of many of the carbon nuclei are shown to be reasonably invariant amongst this series of compounds. A procedure is described for the determination of the (R,S)-epimer ratio of kanamycin A derivatives which have N-substituted groups containing a chiral centre.

Alkylation↗