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Biomedical subjects

S J Gaskell

Publications and source records attributed to S J Gaskell.

At least 91 records · Page 5Linked to original sources
PubMed1985

Trace analysis by gas chromatography/mass spectrometry (GC/MS) using a tandem double-focusing/quadrupole instrument.

Analysis for oestradiol bis-tert-butyldimethylsilyl ether by gas chromatography/mass spectrometry (GC/MS) with selected reaction monitoring ([M]+.----[M-C4H9]+) using a tandem double-focusing/quadrupole instrument gave a detection limit below 10 pg. During analyses of a plasma extract, the selectivity of detection was superior to conventional selected ion monitoring. A parent ion resolution of 5000 was used to eliminate detection of all components but the chosen analyte.

Estradiol↗
PubMed1985

Mass spectrometry in medical research.

This review has sought to emphasise the fundamental principles on which mass spectrometric methods are based in order to indicate not only the present scope of application in medical research but also to suggest areas of future development. Studies with relevance to medical research now span the range from gas analysis to structural studies of proteins. The advent of new ionisation techniques has brought applications which stretch the capabilities of 'traditional' mass analysers (such as magnetic sector instruments) and alternative techniques (time-of-flight, ion cyclotron resonance) are finding increasing favour. Such developments represent, in general, pure research with little immediate impact on clinical practice. Another trend in instrumentation, however, is the development of relatively simple and inexpensive quadrupole mass spectrometers which give adequate performance for gas analyses and rapid GC-MS determinations of drugs or endogenous metabolites. It is likely that this divergent trend in medical mass spectrometry--both to more complex research instruments and to simpler routine instruments for the non-specialist--will continue.

Adrenal Hyperplasia, Congenital↗
PubMed1984

The measurement of tamoxifen and metabolites in the rat and relationship to the response of DMBA-induced mammary tumours.

The concentrations of tamoxifen and two of its metabolites, N-desmethyltamoxifen and 4'-hydroxytamoxifen (metabolite B), have been measured in rat plasma and DMBA-induced tumours using gas chromatography-mass spectrometry. At a dose of 100 micrograms/day all three compounds produced tumour regression and, in the case of tamoxifen, the number and extent of regressions and the inhibition of new tumours were dependent upon dosage. No correlation was observed, however, between tumour regression and the concentrations of tamoxifen or N-desmethyltamoxifen in the plasma of individual animals. When tamoxifen, N-desmethyltamoxifen and metabolite B were measured in oestrogen-receptor-positive tumours a correlation was found between reduction in tumour and the tamoxifen concentration in cytosol fractions. The concentrations of all three compounds in both nuclear and cytosol fractions were higher than could be accounted for by binding to the oestrogen receptor. The mechanistic significance of these high values is, at present, unclear.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1984

Analyses for progesterone in serum by gas chromatography/mass spectrometry: target data for external quality assessment of routine assays.

We describe a procedure for measuring progesterone in plasma and serum by isotope dilution and mass spectrometry. Extraction with use of a microcellulose-coupled antiserum is followed by conversion to the 3-enol heptafluorobutyrate and analysis by gas chromatography/mass spectrometry (GC/MS) with selected ion monitoring, at a resolution of 5000. Interassay CVs were 1.5 to 5.4% for the concentration range 13 to 43 nmol/L. Analyses of various serum volumes showed excellent linearity. Accurate determination of progesterone added to serum was demonstrated. Plasma and serum pools were analyzed to provide target data for use in the U.K. national external quality-assessment scheme for progesterone assays. Direct, non-extraction radioimmunoassays and those incorporating solvent extraction both showed a positive bias with respect to data obtained by the present procedure, but the bias was more marked with the direct assays.

Female↗
PubMed1983

Fast atom bombardment mass spectrometry of steroid sulphates: qualitative and quantitative analyses.

Negative ion mass spectra obtained by fast atom bombardment of glycerol solutions of steroid sulphates include the steroid sulphate anion as the single prominent feature. High sensitivity is achieved, with full spectra obtained for samples of less than 15 ng. Differentiation of the isomeric steroids, dehydroepiandrosterone sulphate and testosterone sulphate, is made by comparison of the products of fragmentation of metastable ions. Analyses of biological extracts suffer from poorly-understood matrix effects which may cause partial or complete suppression of the signal attributable to steroid sulphates. Use of an immunoadsorption extraction technique, however, has permitted the detection and approximate quantification (using a (2H2) analogue as internal standard) of dehydroepiandrosterone sulphate in blood plasma. Interference from glycerol background is avoided by preparation of the pentafluorobenzyloxime derivatives.

Dehydroepiandrosterone↗
PubMed1983

Stability of four steroids in lyophilised human serum.

The stability of a preparation of lyophilised serum and its suitability for use as a reference material for routine assays of cortisol, oestradiol, and progesterone have been studied in four laboratories with a variety of assay systems. Cortisol and oestradiol were also measured by gas chromatography-mass spectrometry. The lyophilised serum was suitable for use in all routine and reference assay methods examined, with between-method variability no greater than that for frozen serum pools. The concentrations of cortisol, oestradiol, and progesterone were predicted by accelerated degradation studies to decline by 0.01% per annum if the preparations were to be stored at --20 degrees C. The testosterone content of the preparation, determined in one laboratory, provided no evidence for degradation. The preparation can be shipped for use at ambient temperature without deleterious effect.

Drug Stability↗
PubMed1983

External quality assessment of assays for cortisol in plasma: use of target data obtained by gas chromatography/mass spectrometry.

We describe procedures for measuring cortisol in plasma and serum by isotope dilution and mass spectrometry. A method that incorporated solvent extraction, derivatization, and gas chromatography/high-resolution mass spectrometry provided data of good precision; interassay CVs were generally 3 to 4% for the concentration range of 100-650 nmol/L. Replacing solvent extraction with extraction on a column of Lipidex 1000 or extraction by immunoadsorption yielded data in excellent agreement with the first method. Plasma and serum pools were analyzed to provide target data for use in the U.K. National External Quality Assessment Scheme for cortisol assays. Routine laboratory assays, as judged by comparison with mass-spectrometric data, were generally positively biased except for analysis of a charcoal-stripped plasma supplemented with cortisol. The results emphasize the importance of using unadulterated plasma or serum pools in assessments of steroid assay procedures.

Charcoal↗
PubMed1983

Immunoadsorption to improve gas chromatography/high-resolution mass spectrometry of estradiol-17 beta in plasma.

We describe a new, highly selective procedure for the determination of estradiol-17 beta in plasma. Samples are extracted with a micro-cellulose-coupled antiserum to estradiol-17 beta. Conversion of the extracted steroid to the bis(trimethylsilyl) ether is followed by gas chromatography/high-resolution mass spectrometry with selected ion monitoring. Precise quantification is achieved through the use of [2H3]estradiol-17 beta as internal standard.

Cross Reactions↗
PubMed1982

Identification and quantification of dehydroepiandrosterone sulphate in saliva.

3 beta-Hydroxy-5-androsten-17-one (dehydroepiandrosterone) sulphate has been separated from an extract of human saliva by ion exchange gel chromatography and identified by high resolution gas chromatography-high resolution mass spectrometry of the tert-butyldimethylsilyl derivative of the neutral steroid obtained by enzymic hydrolysis. Quantitative analyses, employing 7,7-2H-dehydroepiandrosterone sulphate as the internal standard, have indicated concentrations in the saliva of young adult subjects to be generally in the range 0.9-5.7 nmol/l, though concentrations as high as 10.7 nmol/l have been observed.

Adult↗
PubMed1981

Determination of testosterone in plasma from men by gas chromatography/mass spectrometry, with high-resolution selected-ion monitoring and metastable peak monitoring.

Highly specific methods are described for determining testosterone in plasma or serum from men. Extract fractions obtained by selective isolation procedures are converted to tert-butyldimethylsilyl (TBDMS) oximes/TBDMS ethers or methyl oximes/TBDMS ethers and analyzed by gas chromatography/mass spectrometry in the high-resolution selected-ion monitoring or metastable peak-monitoring modes. [2H3]Testosterone and unlabeled 17-epitestosterone are used as the respective internal standards. When we applied the two procedures to analysis of samples of pooled plasma and serum used for external quality assessment of routine assays, the results agreed well. Interlaboratory values for mean concentrations obtained by routine immunoassays (y) consistently exceeded values obtained by our technique (x), although the values closely correlated (r = 0.997; y = 1.008x + 0.564 nmol/L).

Carbon Radioisotopes↗
PubMed1981

Measurement of diethylstilbestrol in plasma from patients with cancer of the prostate.

A specific radioimmunoassay has been developed for diethylstilbestrol (DES), using an antiserum raised against DES monocarboxymethyl ether and a tritium-labeled radioligand. Prior to radioimmunoassay, a fraction enriched in DES is obtained from a dichloroethane extract of plasma using Sephadex LH-20. The specificity of the assay is good, and the sensitivity (130 pg/ml) is adequate for accurate determination of DES in plasma from prostatic cancer patients treated with the drug. The precision is satisfactory, with an interassay coefficient of variation of approximately 10% at concentrations of approximately 1 ng/ml, and the blank values are negligible. Excellent agreement (r = 0.96) is observed between data obtained by radioimmunoassay and those obtained by a procedure using gas chromatography-high-resolution mass spectrometry. DES concentrations in the plasma of six treated (1 mg DES three times daily) patients were in the range 0.15 to 6.0 ng/ml. Increases in plasma concentration were observed within 2 hr of administration, with secondary rises occurring 5 to 6 hr later. Plasma testosterone concentrations were low in four of the patients; in a single subject, relatively high levels of testosterone were further elevated following administration of luteinizing hormone-releasing hormone.

Circadian Rhythm↗
PubMed1980

Analyses of steroids in saliva using highly selective mass spectrometric techniques.

Highly selective techniques of gas chromatography mass spectrometry have been used in the unequivocal identification of salivary steroids at concentrations ranging from 20 pg ml-1 to 20 ng ml-1. Oestradiol-17 beta, for example, has been identified in pregnancy saliva by gas chromatography high resolution mass spectrometry selected ion monitoring of the bis-TMS ether and by gas chromatography mass spectrometry metastable peak monitoring of the bis-tert-butyldimethylsilyl ether. Dehydroepiandrosterone sulphate has been identified in saliva, following enzymic hydrolysis, by gas chromatography high resolution mass spectrometry selected ion monitoring of the tert-butyldimethylsilyl ether and methyloxime tert-butyldimethylsilyl ether. These initial analyses have been designed to guide the development of routine immunoassay procedures which may subsequently be validated by comparison with reference gas chromatographic mass spectrometric methods.

Dehydroepiandrosterone↗
PubMed1980

Analysis of testosterone and dehydroepiandrosterone in saliva by gas chromatography-mass spectrometry.

Testosterone and 3 beta-hydroxyandrost-5-en-17-one (dehydroepiandrosterone) have been identified in human parotid fluid and saliva by gas chromatography-mass spectrometry/selected ion monitoring analyses of the t-butyldimethylsilyl ether and methyl oxime, t-butyldimethylsilyl ether derivatives. High specificity of analysis has been achieved by the use of high mass spectrometric resolution or by the monitoring of metastable peaks. Quantitative analyses indicate concentrations of both unconjugated testosterone and unconjugated dehydroepiandrosterone in the range 200-800 pmol/l in the saliva and parotid fluid of the normal males examined. These represent 1.5-7.5% of the concentrations of the steroids in blood plasma taken from the same subjects.

Dehydroepiandrosterone↗