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Biomedical subjects

A C Moffat

Publications and source records attributed to A C Moffat.

At least 37 records · Page 2Linked to original sources

Application of retention indices based on the alkylarylketone scale to the separation of the local anaesthetic drugs by high-performance liquid chromatography.

The separation of the local anaesthetic drugs by reversed-phase high-performance liquid chromatography using a Hypersil ODS column has been examined in order to identify critical factors in the establishment of a retention database for interlaboratory comparisons. An eluent of methanol-aqueous orthophosphoric acid (15:85, v/v) (pH 2.5) containing 0.7% hexylamine has been used. The effects of small changes in the eluent composition, pH, temperature and the use of different column packing materials on the retentions of the analytes have been studied. The use of capacity factors, relative capacity factors and retention indices based on the alkylarylketone scale have been compared.

Amines↗

Monitoring urine for inhaled cannabinoids.

The current position on the "passive smoking" of cannabis is reviewed with particular reference to the analysis of urine. The pharmacokinetics and metabolism of delta-9-tetrahydrocannabinol are first described, followed by a survey of methods used to identify and quantify its metabolites in urine. Published data concerning the appearance of cannabinoids in urine following "passive smoking" of cannabis are compared and the most important factors described. The problems of interpreting the results of the analysis of urine in forensic cases are discussed and a possible means to clarify the position by means of analysing serum is suggested.

Cannabinoids↗

A collaborative study to investigate the retention reproducibility of barbiturates in HPLC with a view to establishing retention databases for drug identification.

A collaborative study among 10 laboratories has been undertaken to investigate the interlaboratory reproducibility of retention measurements in a high performance liquid chromatographic (HPLC) system for separating barbiturates. The system involved an ODS-Hypersil column with an eluent of methanol:phosphate buffer (40:60, v/v) at pH 8.5; all laboratories used the same batch of packing material. The conventional methods of recording retention properties (retention times and capacity factors) gave poor interlaboratory reproducibility. Better results were obtained by expressing the retentions relative to a standard barbiturate (quinalbarbitone); relative adjusted retention times proved to be more effective than straightforward relative retention times. Retention indices based on the alkylarylketone scale were not as reproducible as the methods based on a single closely related compound. The best reproducibility was obtained using corrected capacity factors based on the retention of four barbiturates in a standard mixture. The results of the study are discussed with a view to selecting the best methods of recording retention in HPLC when considering the establishment of databases for drug identification.

Barbiturates↗

High-performance liquid chromatography systems for the separation of local anaesthetic drugs with applicability to the analysis of illicit cocaine samples.

Two high-performance liquid chromatography (HPLC) systems are presented which are suitable for the separation of local anaesthetic drugs. An octadecyl-silica column is used with aqueous methanolic eluents (15 and 50% respectively) containing n-hexylamine-orthophosphoric acid buffers and data for 36 compounds are given. The HPLC systems have application for the identification of unknown drugs in this class while the first eluent (15% methanol, pH 2.5) is particularly useful for the examination of illicit cocaine samples because it gives good separation of common adulterants and impurities.

Anesthetics, Local↗

High-performance liquid chromatography retention data for 84 basic drugs of forensic interest on a silica column using an aqueous methanol eluent.

High-performance liquid chromatography retention characteristics have been measured for 84 basic drugs of forensic interest using a silica column with a methanol-aqueous ammonium nitrate eluent. The drugs are from two classes of major interest, namely, the narcotic analgesics (including antagonists, metabolites and analogues) and drugs structurally and pharmacologically related to amphetamine.

Amphetamine↗

The decomposition of benzodiazepines during analysis by capillary gas chromatography/mass spectrometry.

A capillary gas chromatography column directly interfaced to a mass spectrometer was used for the analysis of sixteen benzodiazepines. The thermal stability of the drugs was found to be related to their chemical structure. Nine of the benzodiazepines were thermally unstable indicating that care should be taken in the interpretation of gas chromatographic data from this class of drugs. The unstable benzodiazepines were: ketazolam which decomposes to diazepam; N-4 oxides (chlordiazepoxide and demoxepam) which lose an oxygen radical; aromatic 7-nitro compounds (nitrazepam and clonazepam) which are partially reduced to the corresponding amine; alpha-hydroxy ketones (lorazepam and oxazepam) which decompose with the loss of water and N-methyl-alpha-hydroxy ketones (lormetazepam and temazepam) which partially decompose with the loss of a hydrogen molecule to produce the corresponding alpha, beta-diketones. Few problems were encountered in distinguishing the drugs by their mass spectra, the exceptions being ketazolam which decomposes to diazepam and demoxepam which decomposes to desmethyldiazepam. In general, good spectra were obtained from 20-50 ng of drug injected. However, for those compounds where the decompositions were not quantitative (nitrazepam, clonazepam, lormetazepam, temazepam) detection limits were poor.

Benzodiazepines↗

Forensic aspects of the metabolism and excretion of cannabinoids following oral ingestion of cannabis resin.

Following oral ingestion of cannabis resin, delta 9-THC-11-oic acid and its O-ester glucuronide were detected using RIA and combined hplc/RIA and shown to be major plasma metabolites of delta 9-THC. delta 9-THC-11-oic acid was not excreted in the urine in significant concentrations, the glucuronide conjugate being the major urinary metabolite detected. delta 9-THC metabolites were detected in blood for up to 5 days and in urine for up to 12 days following a single oral dose of delta 9-THC (20 mg). Estimates for the half life of delta 9-THC-11-oic acid and its glucuronide in plasma, and total metabolites in urine have been obtained. Interpretation of blood or urine total cannabinoid levels is most difficult, however, drug/metabolite ratios and metabolite/metabolite ratios may have potential for indicating recent cannabis use.

Adult↗

Passive inhalation of cannabis smoke.

Six volunteers each smoked simultaneously, in a small unventilated room (volume 27 950 litre), a cannabis cigarette containing 17.1 mg delta 9-tetrahydrocannabinol (THC). A further four subjects - passive inhalers - remained in the room during smoking and afterwards for a total of 3 h. Blood and urine samples were taken from all ten subjects and analysed by radioimmunoassay for THC metabolites. The blood samples from the passive subjects taken up to 3 h after the start of exposure to cannabis smoke showed a complete absence of cannabinoids. In contrast, their urine samples taken up to 6 h after exposure showed significant concentrations of cannabinoid metabolites (less than or equal to 6.8 ng ml-1). These data, taken with the results of other workers, show passive inhalation of cannabis smoke to be possible. These results have important implications for forensic toxicologists who are frequently called upon to interpret cannabinoid levels in body fluids.

Adult↗

Poisoning-associated deaths for England and Wales between 1973 and 1980.

The annual number of deaths in England and Wales associated with poisoning by solids and liquids over the 8-year period between 1973 and 1980 has remained fairly constant with an average of 2897. Marked trends in the number of deaths associated with specific drugs are evident and apparently reflect prescription trends and drug availability. Barbiturate poisonings dropped steadily following the downward trend in barbiturate prescriptions. Deaths associated with dextropropoxyphene, paracetamol and certain benzodiazepines increased dramatically.

Analgesics↗

Applications of rapid-scanning multichannel detectors in chromatography. Plenary lecture.

A review of progress in the field of multichannel detection in column and thin-layer chromatography is presented, together with some novel applications of a computer-based, linear photodiode array UV--visible spectrophotometer for detection in high-performance liquid chromatography (HPLC). Computer-aided methods for simultaneous monitoring of the elution profile at three wavelengths with automatic peak detection and capture of UV spectra are described. The continuous calculation of absorbance ratios during elution is discussed as an index of peak homogeneity. A novel technique for the enhancement of qualitative identification in HPLC, based on transformation of captured spectra to the second derivative or to the decadic logarithm, is proposed. These developments are exemplified by a model system of diacetylmorphine and its principal metabolites and degradation products, morphine and 6-acetylmorphine. The potential utility of three-dimensional projections of (A, lambda, t) data is discussed in the context of pharmaceutical, bioanalytical and forensic applications.

Chromatography, High Pressure Liquid↗

Amphetamine radioimmunoassay: chemical tuning of specificity.

Four [125I]iodine labelled amphetamine derivatives were synthesised. Three of these proved useful in the development of radioimmunoassays for amphetamine. The assays, all using the same antiserum, had widely differing specificities for compounds closely related to amphetamine. Thus, chemical modification of the radiotracer was used to tune radioimmunoassay specificity without recourse to the production of different antisera.

Amphetamines↗

Quantification of the interaction between barbiturates and alcohol and interpretation of fatal blood concentrations.

Barbiturates and alcohol are frequently found in combination in cases of accidental or intentional fatal self-poisoning. Unfortunately, the lack of any precise knowledge concerning their interaction creates difficult problems when an interpretation of toxicological data is sought. 1 In the following work the joint action of single barbiturates and alcohol is examined and a means of quantifying it is presented. 2 The effects of different amounts of alcohol on fatal amylobarbitone, butobarbitone, pentobarbitone, phenobarbitone and quinalbarbitone blood concentrations are compared. 3 Combined alcohol-barbiturate blood concentration curves connecting those concentration pairs equally effective in causing death are used to quantify the increase in toxicity. The quantitative effects of alcohol appear to be greater with the shorter- and longer-acting barbiturates than with the intermediate-acting derivatives. The different modes of interaction are discussed in terms of the physico-chemical and pharmacokinetic properties of the drugs.

Barbiturates↗