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R F Browner

Publications and source records attributed to R F Browner.

4 recordsLinked to original sources
PubMed2001

Speciation and identification of organoselenium metabolites in human urine using inductively coupled plasma mass spectrometry and tandem mass spectrometry.

A method for speciation and identification of organoselenium metabolites found in human urine samples using high performance liquid chromatography/inductively coupled plasma mass spectrometry (HPLC/ICP-MS) and tandem mass spectrometry (MS/MS) is described. Reversed-phase chromatographic separation was used for sample fractionation with the ICP-MS functioning as an element-selective detector, and six distinct selenium-containing species were detected in a human urine sample. Fractions were then collected and analyzed using a triple quadrupole mass spectrometer with electrospray ionization and collision-induced dissociation to obtain structural information. The first two fractions were identified specifically as selenomethionine and selenocystamine, estimated to be present at approximately 11 and 40 ppb, respectively. To the best of our knowledge, this is the first time these two metabolites have been positively identified in human urine.

Chromatography, High Pressure Liquid↗
PubMed2000

Liquid chromatography/electrospray mass spectrometry of organoselenium compounds with postcolumn crown ether complexation.

Postcolumn addition is an effective means of alleviating or solving ionization-related problems in liquid chromatography/electrospray ionization mass spectrometry (LC/ESIMS). In the current study, initial attempts to develop a direct LC/ESIMS method for an organoselenium compound, 4-hydroxyphenyl 2-methyl-2-aminoethyl selenide (HOMePAESe), were unsuccessful because of extensive fragmentation which occurred even under the mildest in-source collision-induced dissociation (CID) conditions. To reduce the extent of compound fragmentation, a crown ether, 18-crown-6, was added postcolumn to the system, forming a complex with HOMePAESe, which survived the electrospray ionization process with reduced fragmentation and hence improved sensitivity for the major ions. The general applicability of this crown ether complexation approach to clinical samples was demonstrated by the analysis of HOMePAESe in human urine, using a structural analogue, 4-fluorophenyl 2-aminoethyl selenide (FPAESe) as an internal standard. The limit of detection for HOMePAESe, based on a signal-to-noise ratio of 3:1, was estimated to be 5 pg/microL in urine. The potential application of this approach to the general analysis of other amine-containing compounds was also evaluated.

Chromatography, Liquid↗
PubMed1997

An orally active selenium-based antihypertensive agent with restricted CNS permeability.

We report here the first orally active, selenium-based antihypertensive agent, and we demonstrate its restricted CNS permeability using inductively coupled plasma/mass spectroscopy (ICP/MS) and operant behavioral analysis. The biochemistry and pharmacology of selenium are subjects of intense current interest. As a consequence of the redox chemistry of the selenium moiety, phenylaminoalkyl selenides possess the remarkable characteristic of propagating a cycle of turnover-dependent local depletion of reduced ascorbate when processed by the key enzyme of catecholamine metabolism, dopamine-beta-monooxygenase. ICP/MS analysis was used to determine the pharmacokinetic parameters for selenide compounds after i.v. administration to anesthetized rats. Analysis of the data using a two-compartment pharmacokinetic model established very rapid initial clearance and a short beta-elimination half-life from blood. We developed an oxidative procedure for digestion and processing of tissue samples in order to obtain ICP/MS data on the tissue distributions of Se-containing metabolites after the administration of selenide compounds. The results establish that aromatic ring hydroxylation of the selenides results in a marked reduction in brain levels of Se-containing metabolites. The comparative effects of selenide compounds on locomotor activity and operant behavior were then investigated, and the results fully corroborate the ICP/MS analytical results. The novel compound, 4-hydroxy-alpha-methyl-phenyl-2-aminoethyl selenide, exhibits both restricted CNS permeability and oral antihypertensive activity in spontaneously hypertensive rats. This compound is the first orally active selenium-based antihypertensive agent ever reported, and it possesses properties that are highly desirable in pharmacological agents being developed for treatment of chronic diseases such as hypertension.

Administration, Oral↗