Diagnostic exercise. Cutaneous acariasis.
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Biomedical subjects
Publications and source records attributed to E Watson.
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A rapid and highly sensitive method is reported for the quantitative determination of verapamil in plasma. Verapamil and its internal standard are extracted from alkalinized plasma with heptane and then back-extracted into dilute sulfuric acid. An aliquot is injected directly into a high-performance liquid chromatograph, separated by reversed-phase chromatography, and quantified by a fluorescence detector. The procedure is suitable for the routine determination of verapamil in plasma in concentrations as low as 1 ng/ml.
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Procedures are reported for the formation of pertrimethylsilyl and pertrimethylsilyl methoxime derivatives of the aglycones of doxorubicin, daunorubicin, carminomycin, chromomycin A3, and mithramycin. The mass spectra are consistent with the formation of these derivatives. Fragmentation patterns highly specific for these derivatives are proposed, and the potential application for the identification of metabolites of these compounds is discussed.
By using previously developed pertrimethylsilylation and methoxime formation procedures, the GLC--mass spectra of pertrimethylsilyl and pertrimethylsilyl methoxime derivatives of 12 doxorubicin and daunorubicin glycone analogs, mostly synthesized in this laboratory, were studied. The fragmentation pathways were readily interpretable, and the patterns were highly specific for corresponding structural changes, thus supporting the previous contention that this method has potential for the identification of doxorubicin and daunorubicin metabolites. Four aglycone metabolites were identified, on the basis of their GLC--mass spectra, in the hydrolysate of the 1-butanol extract of bile obtained from a doxorubicin-treated rabbit.
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A rapid high-pressure liquid chromatographic assay is described for the analysis of methotrexate (MTX) and its major metabolite, 7-hydroxymethotrexate (7-OH-MTX), in plasma samples from patients following high-dose therapy. The method involves an ion-pair extraction of MTX from plasma with chromatography on a microparticulate anion-exchange column using ultraviolet detection at either 254 or 315 nm. Maximum sensitivity achieved was 1 X 10(-7) M. In addition to being specific for parent MTX, this procedure was used to detect and quantitate significant concentrations of 7-OH-MTX in several patients. Comparison to a protein-binding method indicated a greater degree of specificity for the chromatographic procedure. The procedure can be used to allow therapeutic monitoring of plasma MTX and metabolite for patients receiving high-dose MTX therapy as well as to determine the purity of formulations of MTX used clinically. In addition, the procedure is applicable to the support of pharmacokinetic studies of MTX in animals and man.