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Biomedical subjects

A C Moffat

Publications and source records attributed to A C Moffat.

At least 55 records · Page 3Linked to original sources

Therapeutic, toxic and fatal blood concentration ranges of antiepileptic drugs as an aid to the interpretation of analytical data.

1 Problems associated with the interpretation of analytical results are often related to the ineffective presentation of reference information. Concentration-response curves overcome many of the problems by presenting all available information concisely and by allowing clear comparisons between drug concentrations associated with different pharmacological responses. Although visual comparison of such curves is possible, it can be advantageous to represent them numerically. 2 Numerical representations are used in the present work to compare sub-therapeutic, optimally therapeutic, toxic (side-effects and severe effects), and fatal blood concentrations of the commonly prescribed antiepileptic drugs. 3 Blood drug concentrations accounting for 50% of the population (EC50) are expressed in relation to the concentrations accounting for 10% (EC10) and 90% (EC90) of the population in each clinical category. 4 Such EC10-EC50-EC90 ranges are shown to represent adequately the concentration-response curves. They demonstrate the overlap between drug blood concentrations associated with the various responses and give a good indication of the expected response at any concentration. The concentration ranges are therefore a very useful interpretative aid in therapeutic drug monitoring, emergency toxicology, and forensic toxicology.

Anticonvulsants↗

A collection of therapeutic, toxic and fatal blood drug concentrations in man.

In order to assess the significance of drug concentrations measured in clinical and toxicological investigations, it is essential that good collections of data are readily available. As a guide to interpreting findings, the present work provides a compilation of therapeutic, toxic and fatal blood concentration ranges of 298 drugs of interest to clinical pharmacologists, clinical toxicologists, and forensic toxicologists. Wherever possible, ranges are expressed concisely in terms of the maximum blood concentrations which account for 10, 50 and 90% of the data collected. They provide easy access to the most reliable information which relates the blood drug concentration to the biological response it produces. Where appropriate, the different toxic effects of a drug and/or the different degrees of severity of toxic symptoms associated with different drug levels are clearly defined. The original sources of all data used are provided to allow the analyst to obtain further analytical, pharmacokinetic and toxicological information should this be necessary. Those factors (e.g. age, capacity for drug metabolism, drug interactions, etc) which can modify the relationship between a drug concentration and the response it produces are briefly discussed.

Data Collection↗

Combined high-performance liquid chromatography and radioimmunoassay method for the analysis of delta 9- tetrahydrocannabinol and its metabolites in plasma and urine.

A high-performance liquid chromatography-radioimmunoassay method for the measurement of cannabinoids in plasma and urine is described. The experimental procedure consists of chromatographing a plasma extract or hydrolysed urine sample by high-performance liquid chromatography and quantifying the eluting cross-reacting cannabinoids with radioimmunoassay. The concentrations of delta 9- tetrahydrocannabinol (THC), cannabinol, mono-hydroxylated metabolites, di-hydroxylated metabolites, delta 9-THC-11-oic acid, and delta 9-THC-11-oic acid ester glucuronide may be measured by this technique.

Chromatography, High Pressure Liquid↗

Gas-liquid chromatographic retention indices of 1318 substances of toxicological interest on SE-30 or OV-1 stationary phase.

Retention indices associated with 1318 substances likely to be encountered in toxicological analyses are presented. They are listed in ascending order of retention index for identification purposes and also in alphabetical order of compound name. The 4586 values used in this collection have been extracted from 36 sources, many of which have not been previously published. In many cases, where the quoted retention index is the mean of several determinations, the reproducibility and reliability of this value may be assessed. A histogram of the 1742 values listed is provided to help in determining the usefulness of a retention index for identification purposes. The reproducibility of inter-laboratory retention index measurements for twenty compounds on both SE-30 and OV-17 are presented and show the former, on average, to give more reproducible results.

Chromatography, Gas↗

Analysis of barbiturates in blood by high-performance liquid chromatography.

A high-performance liquid chromatographic (HPLC) assay for the identification and quantification of barbiturates in blood at therapeutic levels had been developed. An ODS-silica column is used with an eluent of 40% methanol at pH 8.5. The barbiturates are detected at 240 nm. The sample preparation procedure involves extraction of unfractionated blood (100 microliter) with hexane-diethyl ether (50 : 50, v/v) ang is very rapid. Talbutal is used as an internal standard. The method has been applied to the determination of five barbiturates (amylobarbitone, butobarbitone, cyclobarbitone, pentobarbitone and quinalbarbitone) in blood after therapeutic doses of the drugs. An application of the HPLC assay to forensic casework is demonstrated.

Barbiturates↗

Analytical aspects of barbiturate abuse: identification of drugs by the effective combination of gas-liquid, high-performance liquid and thin-layer chromatographic techniques.

Chromatographic retention data for a group of barbiturates have been measured on seven chromatographic systems (two gas--liquid chromatographic (GLC), three high-performance liquid chromatographic (HPLC) and two thin-layer chromatographic systems) and the value of these for barbiturate identification has been discussed. The overall correlations observed between pairs of systems are generally low; however, specific groups of barbiturates show very high correlations and this determines the approach to the selection of two or more systems to increase chromatographic discrimination of the barbiturate group. Column chromatographic techniques with lipophilic phases (GLC using SE-30, HPLC using ODS-silica) are most suitable for barbiturate identification. Changes of eluent pH in reversed-phase HPLC proved very effective for the separation of barbiturates with closely related structures.

Barbiturates↗

Gas--liquid chromatographic retention indices of 296 non-drug substances on SE-30 or OV-1 likely to be encountered in toxicological analyses.

The advent of the widespread use of selective detectors (electron capture detector, phosphorus/nitrogen dectector) for gas--liquid chromatography used in toxicological analyses has revealed the presence of hitherto unseen interfering materials. These substances may be conveniently grouped into (1), anti-oxidants; (2), putrefactive and endogenous compounds; (3), pesticides; (4), food additives, flavours and fragrances; (5) plasticisers, plastic additives and vulcanising agents and (6), scintillation reagents. To facilitate the identification of these materials, retention indices on the dimethyl silicone phases SE-30 or OV-1 have been compiled by the two laboratories to include 296 such compounds. Most gave single peaks, but some gave complex patterns indicating that they were mixtures of compounds. Of the 296 compounds, 14 did not give observable peaks, 8 gave 2 or 3 peaks and 44 gave more than 3 peaks. To determine the interlaboratory difference between retention index measurements, 17 compounds were chromatographed by both laboratories: the mean difference was +/- 13 retention index units with only one greater than +/- 50 retention index units. Examples of how these materials may be encountered during toxicological analyses are given. Data are also presented on compounds which have been used as internal standards.

Chromatography, Gas↗