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Biomedical subjects

A C Moffat

Publications and source records attributed to A C Moffat.

At least 19 recordsLinked to original sources

Ketorolac trometamol for postoperative analgesia after orthopaedic surgery.

We have compared the postoperative morphine requirements and analgesic efficacy of four doses of i.m. ketorolac 30 mg administered 6-hourly with placebo in a double-blind study of patients undergoing major or minor orthopaedic surgery. During the 24-h postoperative study period which began at the end of surgery, patients were prescribed i.m. morphine 10 mg as required 2-hourly and assessments were made of pain at 4 and 24 h. After major surgery, the median morphine consumption over 24 h was 10 mg in patients who received ketorolac, compared with 30 mg in those who received placebo (P = 0.008). Visual analogue pain scores and verbal pain assessments were better than placebo at 4 h (P = 0.028 and P = 0.008, respectively), but were not statistically different between the groups at 24 h. Overall assessment of pain was similar in both groups who had undergone major surgery. In the minor surgery groups, median morphine consumption was 0 mg in patients who received ketorolac, compared with 10 mg in those given placebo (ns). Visual analogue pain scores at 24 h after surgery were significantly less in patients who had received ketorolac compared with placebo (P = 0.046) and the overall assessment of pain relief was better in the ketorolac group (P = 0.0007). Mandatory administration of ketorolac appeared to be of benefit in both major and minor orthopaedic surgery, although the principal effects were reduction in requirement for supplementary morphine for major surgery and better overall analgesia for minor surgery.

Adolescent

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

A high-performance liquid chromatography-radioimmunoassay method for the measurement of cannabinoids in urine is described. The method involves chromatographing a hydrolysed urine sample with high-performance liquid chromatography and quantifying the eluting cross-reacting cannabinoids with radioimmunoassay. It has been applied to the analysis of cannabinoids in human urine obtained from subjects who had smoked delta 9-tetrahydrocannabinol and the identities of some of the cross-reacting cannabinoids have been established by gas chromatography-mass spectrometry. The method is suitable for use as a routine procedure for cannabinoid analysis in urine.

Chromatography, High Pressure Liquid

Evaluation of weighted discriminating power calculations as an aid to the selection of chromatographic systems for the analyses of drugs.

In toxicological analyses some chromatographic separations are more important than others. Two weighting methods for chromatographic data are described which incorporate the importance of particular separations into discriminating power calculations. The data were abstracted from a publication on the separations of acidic drugs on thin-layer chromatographic systems. When compared with non-weighted discriminating power calculations, those obtained with the weighting procedure did not give any advantage.

Chromatography, Thin Layer

Choice of thin-layer chromatographic systems for the routine screening for neutral drugs during toxicological analyses.

The efficiencies of fifteen thin-layer silica gel chromatographic systems for separating commonly encountered neutral drugs are compared. The discriminating powers of the systems are measured both individually and in combination. Chloroform-acetone (4:1) is found to be the best system. The combination of the ethyl acetate-methanol-ammonia (85:10:5) system with this gives the best pair of systems. A suitable sequence of spray reagents is also suggested. The chloroform-acetone (4:1) system is recommended as the best system to use when screening for both acidic and neutral drugs.

Chromatography, Gel

Choice of thin-layer chromatographic systems for the routine screening for acidic drugs during toxicological analyses.

The efficiencies of fifteen thin-layer silica gel chromatographic systems in separating commonly encountered acidic drugs are compared. The discriminating powers of the systems are measured both individually and in combination. Ethyl acetate and chloroform-methanol (9:1) are found to be the two best systems. The combination of the ethyl acetate-methanol-ammonia (85:10:5) system with either of these gives the best pair of systems. Various sequences of spray reagents are also examined.

Chromatography, Thin Layer

Combined high-pressure liquid chromatography and radioimmunoassay method for the quantitation of delta 9-tetrahydrocannabinol and some of its metabolites in human plasma.

A high-pressure liquid chromatography-radioimmunoassay (HPLC-RIA) method for the measurement of cannabinoid levels in plasma is described. The method is capable of quantifying 0.1 ng of a cannabinoid in 1 ml of plasma. The experimental procedure consists of an initial separation of cannabinoids in a plasma extract by HPLC followed by collection of the HPLC eluate and RIA. A chromatogram consisting of the cross-reacting cannabinoids in plasma may then be constructed. The plasma concentrations of cannabinoids with retention volumes equivalent to those of delta 9-tetrahydrocannabinol, cannabinol and mono-hydroxylated metabolites have been measured by this technique.

Chromatography, Gas

Analysis of LSD in human body fluids by high-performance liquid chromatography, fluorescence spectroscopy and radioimmunoassay.

A scheme of analysis is described in which the particular advantages of high-performance liquid chromatography (HPLC), fluorescence spectroscopy and radioimmunoassay (RIA) are exploited to the greatest effect. RIA affords a rapid and sensitive preliminary screening method, while the subsequent HPLC analysis using fluorimetric detection yields quantitative chromatographic evidence together with characteristic fluorescence spectra. Fractionation of samples by HPLC followed by RIA of the fractions gives further confirmation of the presence of LSD and its metabolites. The combined methodology has been applied to the analysis of LSD in body fluids for forensic and clinical purposes. Levels down to 0.5 ng of LSD per ml can be detected using the minimum of sample.

Chromatography, High Pressure Liquid

Photochemical detection in high-performance liquid chromatography and its application to cannabinoid analysis.

A novel technique of on-line photochemical derivatization is described which can enhance considerably both the sensitivity and specificity of detection in high-performance liquid chromatography (HPLC).. Material eluting from the column is irradiated with a high flux of UV light, which may induce a reaction to form fluorescent or highly UV-absorbing products. The irradiated eluent then passes into a suitable detector. The photochemical reactor as a neglible effect on resolution, and reaction is achieved in 1-5 sec. An example of the use of this technique is in the detection of cannabinol CBN), a component of cannabis, which is converted into a highly fluorescent compound on irradiation with UV light. Thus, if a sample containing CBN is chromatographed and the column eluent irradiated, CBN can be detected (as the fluorescent photoproduct) with a sensitivity of less than 1 ng. If the chromatogram is then repeated without UV irradiation, only naturally fluorescent products are detected. A compairson of the two chromatograms allows these to be eliminated and leads to a very high specificity for the method. This approach is being developed as the basis of a rapid, sensitive and specific method for the detection of cannabinoids in body fluids. It is expected, however, that photochemical derivatization will extend the use of HPLC to many substances that cannot be satisfactorily detected at present.

Cannabinoids

Radioimmunoassay of lysergic acid diethylamide (LSD) in serum and urine by using antisera of different specificities.

We raised high-titre antisera to two LSD-bovine serum albumin conjugates, one linked via the indole nitrogen, the other via the amide side-chain. The antisera were specific for different parts of the LSD molecule, as demonstrated by cross-reactivity studies with LSD, its metabolites, ergot alkoloids, and closely related compounds. The antisera were used to develop a double-antibody radioimmunoassay with a detection limit of about 0.4 mug of LSD per liter of unextracted urine or serum. We saw no nonspecific interference by urine, serum, or from a series of commonly used drugs. There was good correlation between immunoassay values obtained with the two antisera (r = 0.91). However, the antiserum linked via the indole nitrogen gave consistently higher results for samples from persons who had taken LSD, owing to greater cross-reactivity with LSD metabolites. Radioimmunoassay by use of two such antisera is a more specific screening procedure for LSD abuse than has been available previously. In addition, antisera cross-reacting with LSD metabolites allow measurement of these compounds, for which there is no satisfactory method at the concentrations found in biological fluids in man.

Antibody Specificity

High-pressure liquid chromatography of drugs. II. An evaluation of a microparticulate cation-exchange column.

A microparticulate cation-exchange column has been evaluated for the chromatography of thirty compounds selected as representative of a wide variety of drug substances. Although the column exhibited a strong partition effect besides the expected ion-exchange mechanism, the retention of drugs could be predictably influenced by variation of the eluent ionic strength and organic solvent content. For acidic drugs the column showed little selectivity (although a salting-out effect increased retention at high eluent ionic strengths), but for basic substances Partisil SCX may afford a useful separative medium offering reasonable chromatographic efficiency (HETP is approximately 0.1 mm). The column longevity, however, is at present questionable.

Cation Exchange Resins

High-pressure liquid chromatography of drugs. An evaluation of an octadecylsilane stationary phase.

The performance of a commonly used high-pressure liquid chromatographic stationary phase, octadecylsilane, has been evaluated for 30 compounds selected as representative of a wide variety of drug substances. Chromatographic behavior is found to be highly predictable on the basis of pKa and partition coefficient, and the stationary phase should be especially valuable for the separation of acidic and neutral drugs. For basic drugs, however, the column efficiency is poor, detracting from the overall usefulness.

Amines