Search PubMed⌕ Search

Biomedical subjects

M Scheinin

Publications and source records attributed to M Scheinin.

208 records · Page 12Linked to original sources
PubMed1983

Simultaneous determination of 3-methoxy-4-hydroxyphenylglycol, 5-hydroxyindoleacetic acid, and homovanillic acid in cerebrospinal fluid with high-performance liquid chromatography using electrochemical detection.

An improved high-performance liquid chromatographic method with electrochemical detection (HPLC-EC) for the simultaneous determination of 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA) in cerebrospinal fluid (CSF) of humans and nonhuman primates is described. Quantitation is based on the use of an internal standard, 5-fluoro-HVA. Sample preparation consists of mixing an aliquot of CSF with a solution of the internal standard followed by ultrafiltration. The precision of the method is high, with within-run and between-run coefficients of variation of 2-6% and less than 10%, respectively, in the concentration ranges of the metabolites encountered in human lumbar CSF. Accuracy was tested by comparing the present HPLC method with specific gas chromatographic-mass spectrometric (GS-MS) assays for MHPG and HVA and a GC-MS-validated HPLC assay for 5-HIAA: the correlations obtained were 0.968 for MHPG, 0.989 for 5-HIAA, and 0.999 for HVA, with no systematic bias between the methods. The use of ascorbate as a preserving agent for monoamine metabolites in CSF was not found to be necessary when proper care was exercised in sample handling and storage. The analysis of samples with up to 2% ascorbic acid was possible as well, but MHPG had to be assayed separately using an extraction procedure and an alternative internal standard, 3-ethoxy-4-hydroxyphenylglycol.

Animals↗
PubMed1983

Rapid and simple determination of homovanillic acid in plasma using high performance liquid chromatography with electrochemical detection.

A rapid, yet highly reliable, procedure for determination of homovanillic acid (HVA) in plasma is described. After precipitation of proteins with perchloric acid, separation of sample components is directly achieved with high performance liquid chromatography on a reversed-phase column (C8), followed by quantitation based on electrochemical detection. The sensitivity of this method is 0.5 pmol/injection. Detector response is linear from the limit of detection to at least 0.5 nmol/injection. The intra-assay coefficient of variation is 2.2% in the concentration range of 50-150 pmol/ml plasma. The inter-assay coefficient of variation is 6.3%, based on determinations on 30 working days. A comparison of the present method and a specific gas chromatographic-mass spectrometric assay showed good agreement between the two procedures. One chromatographic run requires less than 16 min. for plasma and 10 min. for a standard.

Chromatography, High Pressure Liquid↗
PubMed1982

Application of radioreceptor assay of benzodiazepines for toxicology.

A radioreceptor assay (RRA) for determining benzodiazepines (BZ) has been developed and applied to toxicological analysis of serum from 21 patients with acute BZ overdosage. The method was sensitive (e.g., lorazepam 17 nM, diazepam 41 nM), and specific for pharmacologically active BZ derivatives. The reproducibility of the results was good (intra-assay variation less than 8%, inter-assay variation less than 10%). Concentrations measured by the RRA showed a good correlation with those obtained by gas-liquid chromatographic analysis of the same samples. The quantitative results represent the sum of one or several parent substances and all biologically active metabolites, in proportion to their receptor binding affinities.

Animals↗
PubMed1980

Single dose pharmacokinetics of doxepin in healthy volunteers.

The pharmacokinetics of orally administered doxepin (50 mg) was studied in 8 healthy volunteers. Doxepin (DOX) and desmethyldoxepin (DDOX) concentrations in serum (or plasma) and red blood cells (RBCs) were measured by radioimmunoassay. Peak serum concentrations of DOX were observed at 1-2 hours and they ranged between 59.1-107.4 nmol/1. DOX disappearance was biphasic with a mean distribution half-life of 2.0 hrs and elimination half-life of 17.9 hrs. The mean total apparent volume of distribution was 22.7 l/kg and plasma clearance 0.93 l/hr/kg. The estimated mean first-pass metabolism of DOX was 71% assuming complete absorption. Peak DDOX concentrations were observed at 1-6 hours and they ranged between 35.0-117.8 nmol/l. DDOX elimination was monophasic with a mean apparent half-life of 28.5 hours. Equilibrium dialysis gave a mean protein binding of 75.5% for DOX and 76.0% for DDOX. A highly time dependent and interindividually variable RBC/plasma concentration ratio was observed for both substances. Initially the plasma concentrations were 3-4 times higher than the respective RBC concentrations, but at later time points more DOX and DDOX could be found from the RBCs than from plasma. The major reason for this seemed to be a slower elimination of both drugs from the erythrocytes than from plasma.

Administration, Oral↗
PubMed1980

Radioimmunoassay for doxepin and desmethyldoxepin.

A simple and sensitive radioimmunoassay (RIA) for the determination of doxepin and desmethyldoxepin in plasma or serum has been developed using a previously reported antiserum to the tricyclic anti-depressants. Before assay, doxepin is separated from desmethyldoxepin with selective extraction at different pH values enabling each to be measured specifically. 3H-imipramine is used as tracer. By using the extraction procedure doxepin and desmethyldoxepin concentrations can be measured down to 9 nmol/1 from a 0.1 ml sample. If necessary, sensitivity can be doubled by taking a 0.2 ml sample to extraction. Recoveries of doxepin and desmethyldoxepin were quantitative when the drugs were added at different concentrations to normal, pooled human plasma and the inter- and intra-assay coefficients of variation did not exceed 9%. The concentrations obtained from patient samples by the present RIA correlated well with those by high-pressure liquid chromatography. The RIA was also shown to be useful in pharmacokinetic single dose studies with doxepin.

Antibody Specificity↗
PubMedDate not supplied

A series of 6-(omega-methanesulfonylthioalkoxy)-2-N-methyl- 1,2,3, 4-tetrahydroisoquinolines: cysteine-reactive molecular yardsticks for probing alpha2-adrenergic receptors.

A series of 6-(omega-methanesulfonylthioalkoxy)-2-N-methyl-1,2,3, 4-tetrahydroisoquinolines (7a-d) was prepared and characterized as SH-reactive molecular yardsticks useful in probing alpha2-adrenergic receptors. Rapid displacement of the methanesulfonyl group by a cysteine residue in dilute aqueous solution with concomitant formation of a disulfide conjugate was verified by MALDI-TOF mass spectrometric analysis of the reaction of 7a with a cysteine-containing decapeptide. 7a-d all showed a marked affinity for the three different variants of human alpha2-adrenergic receptors: H alpha(2A)wt, H alpha(2B)wt, and mutant H alpha(2A)Ser201Cys197. However, only the mutated receptor (H alpha(2A)Ser201Cys197) was irreversibly inactivated, and the extent of inactivation in this case was linearly dependent on the length of the side chain of 7a-d. These results show that the molecular yardstick approach tested here can provide useful information for modeling receptor proteins.

Animals↗
PubMedDate not supplied

Determination of maprotiline and N-desmethylmaprotiline from biological fluids by HPLC.

A reversed-phase high-performance liquid chromatographic method has been developed for the simultaneous quantitation of maprotiline and its desmethylated metabolite from biological fluids. In this method, the samples were washed with hexane at acidic pH and then extracted with the same solvent at alkaline pH in the presence of an amine carrier. The drugs were eluted from the C18 column with acetonitrile (30%) in phosphate buffer (pH 2.5) and detected by their UV-absorbances at 205 nm. Peak identification was based on retention times and desmethyldoxepine was used as an internal standard for quantitation. Possible interferences were few; sensitivity (detection limit, 11 nmoles/L) and reproducibility (CV 2-2.5%) were good. Only about 10 minutes of chromatographic time was needed for one sample. Application for screening toxic drugs is suggested and briefly discussed.

Anthracenes↗
PubMedDate not supplied

Plasma levels of atrial natriuretic factor and catecholamines in endotoxin shock in dogs.

Changes in arterial plasma levels of atrial natriuretic factor and catecholamine release were studied in 11 beagle dogs during pentobarbital anesthesia. Seven dogs were injected intravenously with Escherichia coli endotoxin, 0.5 mg/kg over 15 min. Four control dogs received only saline solution. The endotoxin injection resulted in cardiac depression,, hemoconcentration, acidosis and renal hypoperfusion. The central venous pressure remained relatively unchanged in both groups during the 2-hour study. The concentrations of epinephrine, norepinephrine and the norepinephrine metabolite 3,4-dihydroxyphenylglycol increased in arterial plasma during the acute hypodynamic endotoxin shock. In the control dogs the levels of these hormones remained very low and constant. Increased circulating levels of atrial natriuretic factor were observed in endotoxin shock with renal hypoperfusion, unchanged central venous pressure and no concomitant tachycardia.

Animals↗