Biomedical subjects
Publications and source records attributed to R G Reid.
Two serotonin conjugates, N-(trans-p-coumaroyl)-serotonin (1) and N-(trans-feruloyl)-serotonin (maoschamine, 2), isolated from the methanol extract of the seeds of Centaurea nigra, have been assessed for antibacterial and free radical scavenging activities. The general toxicity of 1 and 2 has also been determined by the brine shrimp lethality bioassay.
BACKGROUND: The quality of medicines available in some less-developed countries is inadequate in terms of content of active ingredient. Reasons for the poor quality of drugs include widespread counterfeiting of medicines in less-developed countries, excessive decomposition of active ingredient as a result of high temperature and humidity, and poor quality assurance during the manufacture of medicinal products. Our aim was to investigate the quality of different drugs obtained from retail pharmacies in two urban areas of Nigeria, and, in instances of poor quality, to ascertain the reason why. METHODS: We randomly collected 581 samples of 27 different drugs from 35 pharmacies in Lagos and Abuja in Nigeria. We analysed the medicines for drug content by validated chromatographic methods, and compared our results with pharmacopoeial requirements. FINDINGS: 279 (48%) samples did not comply with set pharmacopoeial limits, and this proportion was uniform for the various types of drugs tested. Although some preparations contained no active ingredient, most had amounts just outside the pharmacopoeial limits. We identified samples with both too much and too little active drug content. INTERPRETATION: The most probable cause of the poor quality of drugs is absence of adequate quality assurance during manufacture. Substandard drugs sold in the pharmacies of less-developed countries could contribute to global microbial resistance and therapeutic failure of infectious diseases.
The method of applying large sample volumes in micellar electrokinetic chromatography termed sweeping is applied to determine the conservative limits of detection of some basic drugs in plasma and urine. The biguanides proguanil, 4-chlorophenylbiguanide and cycloguanil are used as models of basic drugs and the limits of detection obtained compared with those previously reported for capillary zone electrophoresis using field-amplified sample injection (FASI) and also by LC using off-line preconcentration. It is found that the sweeping method can be applied to extracts of such biological matrices. The limits of detection obtained by sweeping are improved over FASI for plasma but not for urine and the limits of detection are higher than those reported for LC, for these compounds.
A chromatographic method is described for the determination of sodium artesunate in plasma. This includes cetyltrimethylammonium bromide as a cationic pairing ion in a reversed-phase system using an octadecylsilica 100 x 4.6 mm I.D. 3 microm analytical column with a mobile phase of acetonitrile/acetate buffer at pH7. Column switching incorporating a 5 microm octadecylsilica 100 x 4.6 mm I.D. precolumn is used in addition to off-line solid-phase extraction for pretreatment of plasma samples in order to eliminate interference from endogenous components. Detection is by post-column derivatisation with 1.0 M methanolic KOH followed by UV detection at 289 nm. Calibration is linear over the range 100-1600 ng ml(-1) and the limit of detection is estimated as 20 ng ml(-1). Illustrative results are shown of the artesunate plasma levels determined by the proposed method following the administration of artesunate as tablets and as suppositories to healthy volunteers.
A reversed-phase HPLC method previously developed for the analysis of progesterone and its major metabolites has been transferred successfully to a capillary electrochromatography (CEC) system. Procedures for fabricating packed capillaries and the modifications made to the capillary electropherograph which allow operation in the CEC mode without pressurisation are described. The dependence of electroosmotic flow on electric field strength, pH and organic modifier content is discussed. Direct comparison with HPLC shows that CEC provides useful gains in efficiency and speed of analysis and requires vastly reduced amounts of both chromatographic phases and material for analysis. On-line concentration is described which allows the lower sensitivity of CEC to be offset by injecting analytes from a non-eluting solution. Examination of steroids in plasma demonstrates that the superior separation by CEC is maintained in a complex biological matrix.
A method for the specific determination of three quaternary ammonium compounds, benzalkonium chloride, cetylpyridinium chloride and dequalinium chloride, used as antibacterial agents in candy-based lozenges, is described based on capillary zone electrophoresis. It is shown that, following optimisation of buffer composition with respect to organic modifier concentration. pH and buffer concentration together with the inclusion of sodium dodecylsulphate as an ion-pairing agent in the case of dequalinium chloride, these analytes migrate in less than 5 min. The resultant electrophoretic peaks are sharp and readily quantified. The individual alkyl components of benzalkonium chloride can be resolved as can related impurities in dequalinium chloride lozenges. The quantitative characteristics of the assay method, based on peak areas normalised with respect to migration times, are reported and the method is compared with a previously published method based on liquid chromatography.
A literature survey on published reports of the determination of drugs in biological fluids shows that all methods of sample pretreatment have been used and that the limits of detection achieved vary widely, ranging from low ngcm(-3) to microgcm(-3). The most widely used injection method was hydrodynamic and, in the majority of cases, whenever low detection limits were achieved, this was a result of preconcentration during the sample pretreatment. Only a small proportion of the reported methods employed electrokinetic injection and utilised the field amplified sample injection (FASI) techniques. An experimental investigation of the alternative hydrodynamic and electrokinetic injection methods for a small set of antimalarial drugs is reported. It was found that electrokinetic injection with FASI from an acetonitrile-water matrix produced dramatic improvements in detection limits. This improvement could not, however, be achieved when the drugs were in plasma using protein precipitation, liquid-liquid extraction or solid phase extraction pretreatment methods. This highlights the importance of sample pretreatment in utilising the potential sensitivity of capillary electrophoresis with electrokinetic injection.
The retention behavior of the quaternary ammonium compounds benzalkonium chloride, cetylpyridinium chloride and dequalinium chloride on a 100 x 4.6 mm id cyanopropyl stationary phase column is reported as a function of organic modifier and ionic hydrophobic mobile phase additive concentrations. Optimum liquid chromatographic mobile phases using different mobile phase additives are reported which are suitable for the determination of cetylpyridinium chloride and dequalinium chloride in a variety of candy-based lozenge formulations. The quantitative aspects of assays based on the separation of active ingredients and formulation excipients were established. The generality of application of the assay methods was evaluated by determining the quaternary ammonium content of different lozenges and comparing the values obtained with the stated dose.
A method for the separation of a mixture of opiates comprising pholcodine, 6-monoacetylmorphine, morphine, heroin, codeine and dihydrocodeine by capillary electrophoresis using a running buffer of 100 mM disodium hydrogenphosphate at pH 6 is described. The characteristics of an analytical method based on this separation for the determination of these drugs following extraction from urine and using levallorphan as internal standard are reported. Detection limits in the region of 10 ng cm-3 are achieved when using electrokinetic injection. A comparison is made of the sensitivity and reproducibility of electrokinetic and hydrodynamic injection for these drugs. Data are presented to show the results obtained when the proposed method is applied to urine spiked with all the above opiates and also to urine from a subject following consumption of dihydrocodeine and pholcodine. The concentrations found are compared with those obtained by LC.
This report describes some of the quantitative aspects of the CZE separation of proguanil, chloroquine and their respective metabolites, the separations of which, by CE and MEKC, were reported in Part 1. Results obtained on the precision of migration time and peak areas using the alternative injection methods of vacuum and electrokinetic are described and discussed. The increase in concentration sensitivity using electrokinetic injection with an organic injection solvent reported in Part 1 is confirmed and the resultant limits of detection in urine reported. An assay method for these compounds in urine is described which incorporates a pretreatment stage of solid phase extraction and the main analytical parameters used in the validation of such an assay are reported. The limitation of the sample pretreatment used when applied to matrices of plasma and saliva are reported and discussed in the context of the electrokinetic injection method used.
A high-performance liquid chromatography (HPLC) assay was developed for ciprofloxacin and sulphadiazine in Isosensitest broth. Combining the HPLC assay with cell dry-weight determinations indicated that both compounds were able to enhance the uptake of the other by log phase Pseudomonas aeruginosa cultured in the presence of the compounds. It is hypothesized that the increased bacterial uptakes are the reason for the enhanced antibacterial activity previously reported for combinations of ciprofloxacin and sulphadiazine.
A reversed-phase isocratic high-performance liquid chromatographic method for the determination of total teicoplanin in plasma is reported. The method developed uses a bracketing injection technique in conjunction with large injection volumes on a 1 mm diameter column to form a limited injection-generated gradient. The chromatography yields adequate resolution among all the major components for individual quantitation and also allows quantitation of total teicoplanin in plasma using ultraviolet detection. Pretreatment is by solid-phase extraction which uses C8 Bond Elut cartridges and gives effective clean up from endogenous materials. The method offers a faster and simplified means to determine total teicoplanin in plasma than those previously reported, and has a detection limit of 50 ng/ml.
A separation of progesterone and its metabolites 17 alpha-hydroxyprogesterone, 20 alpha-hydroxy-4-pregnen-3-one, androstenedione and testosterone by high-performance liquid chromatography with a ternary solvent system is demonstrated. It is found that using a 100 X 1 mm microbore column, higher sensitivity is obtained in the ultraviolet detection of these compounds by using conventionally sized flow cells despite the higher efficiency resulting from the use of a micro-flow cell. It is also shown that, when a non-eluting solvent is used for injection, large injection volumes do not reduce column efficiency, and a 14-fold increase in sensitivity is obtained with a 1-mm column in place of one 4.6 mm in diameter. Using solid-phase extraction and concentration of the sample as pretreatment, progesterone and its hydroxylated metabolites are determined in 0.5-ml samples of rat plasma. The progesterone levels are compared with those obtained by radioimmunoassay.
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A simple method for the extraction of alpha1-fetoprotein from fetal serum in high yield and of sufficient purity for use as radio-iodinated tracer in a radioimmunoassay is described. The purified alpha1-fetoprotein formed aggregates during storage. The presence of 125I-labelled aggregates affected the double antibody radioimmunoassay by increasing the non-specific bound, resulting in decreases assay sensitivity. Freshly prepared 125I-labelled monomer alpha1-fetoprotein is prepared for each assay. The radioimmunoassay described is sensitive to between 100 and 200 pg per tube. Normal adult serum levels were found to be in the range from less than 1 mug/l to 16 mug/l.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.