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M P Kullberg

Publications and source records attributed to M P Kullberg.

16 recordsLinked to original sources

Quantitative determination of dextromethorphan and three metabolites in urine by reverse-phase high-performance liquid chromatography.

A high-performance liquid chromatographic (HPLC) method for the quantitation of dextromethorphan (I) and its three metabolites, dextrorphan (II), 3-hydroxy-9 alpha,13 alpha,14 alpha-morphinan (III), and 3-methoxy-9 alpha,13 alpha,14 alpha-morphinan (IV), in urine was developed. For the analysis of nonconjugated compounds, urine samples at pH 11-11.5, containing 3-methoxy-17-methyl-10-oxo-9 alpha,13 alpha,14 alpha-morphinan as an internal standard, were applied to an extraction column, and the compounds were eluted with 10% n-butyl alcohol-hexane. The organic eluant was extracted with 0.1 M HCl, and an aliquot of the acidic extract was analyzed by HPLC utilizing a 5-micron phenyl column (25 X 0.46-cm i.d.) with a mobile phase of 10 mM potassium phosphate-acetonitrile (45:55, pH 4.0); the column effluent was monitored by UV detection at 280 nm. Free and conjugated metabolites in the enzyme-treated urine were analyzed by selective extraction of I and IV with hexane from urine samples at pH greater than 12 and extraction of II and III with 10% n-butyl alcohol-hexane from urine samples at pH 11-11.5. The minimum quantifiable levels of I-IV ranged from 0.017 to 0.09 micrograms of base/mL and from 0.11 to 0.21 micrograms of base/mL in nonhydrolyzed and hydrolyzed urine, respectively.

Chromatography, High Pressure Liquid↗

The analysis of arildone in plasma, urine and feces by gas--liquid chromatography with electron-capture detection.

The analysis of arildone in plasma, urine and feces by gas--liquid chromatography with electron-capture detection is described. O-(2,3,4,5,6-Pentafluorobenzyl)hydroxylamine is the derivatizing agent for the plasma and urine analysis; 3-nitrophenylhydrazine is utilized for fecal analysis. The mean (+/- S.E.) minimum quantifiable level of arildone was 1.4 (+/- .02) ng/ml in urine, 6.4 (+/- 0.1) ng/ml in plasma, and 12.6 (+/- 1.0) ng/g in feces. The chromatographic response was linear in the range of 0 and 10--120 ng/ml for plasma, 0 and 2.5--20 ng/ml for urine and 0 and 25-250 ng/g for feces. The estimated overall precision of the assay was 5.5%, 64% and 8.9% in urine, plasma and feces, respectively.

Antiviral Agents↗

Amrinone metabolism.

High-performance liquid chromatographic methods for the analysis of amrinone in plasma and for both amrinone and its N-acetyl metabolite in urine were developed and applied to measure specimens obtained from a number of healthy men who had received intravenous or oral amrinone. The intravenous doses ranged from 0.8 to 2.2 mg/kg. Terminal elimination of amrinone from the bloodstream followed apparent first-order kinetics. Half-life, after the drug had distributed to the tissues, was estimated by a log-linear least-squares regression; mean half-life was 2.6 +/- 1.4 hr. During the first 24 hr after medication, unchanged amrinone excreted in the urine of these subjects represented 10% to 40% of the dose. N-Acetyl metabolite in the urine represented less than 2% of the dose. In the oral study, doses ranged from 25 to 250 mg (0.31 to 3.5 mg/kg) and the maximum plasma concentration attained was proportional to the dose. The first order terminal elimination half-life was possibly dose-related. In only one subject were there unequivocal amounts of the N-acetyl metabolite in the plasma.

Aminopyridines↗

Analysis of mepivacaine, bupivacaine, etidocaine, lidocaine, and tetracaine.

A GLC method, employing a nitrogen-phosphorus-sensitive detector, is described for the analysis of mepivacaine, bupivacaine, etidocaine, lidocaine, and tetracaine in biological fluids. The method is simple, reliable, and sensitive, with a practical limit of sensitivity of approximately 2.5 ng/ml, well below therapeutic plasma levels. Extensive start-up procedures and sample preparation are not required.

Acetanilides↗

High-performance liquid chromatographic analysis of rosoxacin and its N-oxide metabolite in plasma and urine.

A high-pressure liquid chromatographic method for the analysis of rosoxacin and its pyridyl N-oxide metabolite in plasma and urine extracts is described. A statistical evaluation of the assay data has shown acceptable accuracy and precision for 0.5 to 25 microgram of rosoxacin or the metabolite per ml of plasma and for 2.5 to 60 microgram/ml of either compound in urine. The minimum quantifiable level for rosoxacin was 0.13 microgram/ml in plasma and 0.64 microgram/ml in urine; for the metabolite in plasma and urine, the corresponding values were 0.21 and 0.60 microgram/ml, respectively. The method was applied to plasma and urine from three dogs medicated orally with 5 mg/kg of rosoxacin. The pharmacokinetic parameters calculated for rosoxacin were: plasma halflife, 1.9 h; plasma clearance, 65 ml/min; volume of distribution, 11.31. The average total urinary excretion of rosoxacin as free and conjugated rosoxacin and its free N-oxide was 7.7 +/- 0.2% over the 48-h collection period.

4-Quinolones↗

Analysis of cyclazocine in plasma.

The analysis of plasma cyclazocine by two methods is described. The radioimmunoassay employed a 125I-labeled radioligand, rabbit antiserum, and sepration of bound from free cyclazocine with a second antibody. The radioimmunoassay was specific for cyclazocine and had a detection limit of approximately 20 pg/ml. The GLC method employed a mass spectrometer as the detector and had a detection limit of approximately 109 pg/ml. Both techniques had acceptable accuracy and precision when used to quantitate cyclazocine in dog and human plasma. The methods were used successfully to quantitate cyclazocine from beagle hounds receiving 0.5 mg of 3H-cylazocine/kg iv. The decline in plasma cyclazocine fitted a two-compartment body model with a mean plasma clearance rate of 39.2 liters/hr.

Animals↗

High-performance liquid chromatographic determination of plasma and urinary 1-ethyl-1,4-dihydro-4-oxo-1,8-naphthyridine-3,7-dicarboxylic acid.

A high-performance liquid chromatographic method for the analysis of 1-ethyl-1,4-dihydro-4-oxo-1,8-naphthyridine-3,7-dicarboxylic acid (I) in plasma and urine is described. A statistical evaluation of the assay technique has shown acceptable accuracy and precision at concentrations as high as 2.0 microgram/ml of plasma or 29.0 microgram/ml of urine for samples augmented with 1. As little as 0.08 microgram/ml of I in plasma or 0.42 microgram/ml of I in urine were quantitatively determined. The mean relative error for the assay of unknown concentrations of I in plasma and urine was +/- 8% and +/- 3%, respectively. This method was used for the analysis of I in the plasma and urine of rhesus monkeys following oral administration of 200 mg/kg of nalidixic acid.

Animals↗

Etrophine in man. II. Detectability in urine by common screening methods.

A single highly euphorogenic dose of etorphine, 100 mug, was administered subcutaneously to 7 nontolerant subjects, and all urine samples were collected for 1 day prior to and 3 days following drug administration. Samples were analyzed for the presence of opiates by radioimmunoassay (Abuscreen) and homogeneous enzyme immunoassay (EMIT), with cutoffs for "ositives" of 40 and 500 ng/ml, respectively. Samples were analyzed for etorphine by thin-layer chromatography (TLC) with iodoplatinate preceded by XAD-2 resin extraction (sensitivity = 0.2 mug etorphine/ml of urine) and by gas-liquid chromatography (GLC) preceded by organic solvent extraction and trimethylsilyl derivatization (sensitivity = 0.1 mug etorphine/ml of urine). The last pre-drug and first two post-drug samples were also analyzed after acid hydrolysis by TLC and after glucuronidase hydrolysis by TLC and GLC. No sample gave a "positive" opiate result in either immunoassay, and no etorphine was detected in the TLC and GLC analyses of any urine sample. Thus, it is unlikely that the abuse of etorphine could be diagnosed by urinalysis using the common screening methods of radioimmunoassay, EMIT, TLC preceded by XAD-2 resin extraction, or GLC preceded by organic solvent extraction and trimethylsilyl derivatization.

Adult↗

An electron spin resonance study of synaptosome opiate receptors. The preparation and use of a spin labeled morphine.

Morphine spin labeled on the phenolic hydroxy group has been prepared using commercially available reagents and characterized by thin layer chromatography, mass spectroscopy, and electron spin resonance spectroscopy. It has been shown that morphine modified in this way retains some opiate activity, does not pass through the blood-brain barrier, and specifically binds to isolate rat brain synaptosomes. Spin labeled morphine has been shown to be an effective biophysical probe complementing radioactive tracer techniques in the study of the narcotic receptor site.

Animals↗

Analysis of iosulamide in plasma and urine: application to intravenous pharmacokinetics in rhesus monkey.

A sensitive, specific, high-performance liquid-chromatographic method for the determination of iosulamide in plasma and urine is described. The method was used to determine pharmacokinetic parameters of iosulamide after intravenous administration to rhesus monkeys. The mean (+/- SE) distribution and disposition half-lives were 0.19 (+/- 0.03) and 1.5 (+/- 0.3) hr, respectively. The mean (+/- SE) model-dependent and model-independent volumes of distribution at steady state were 0.41 +/- (0.078) and 0.49 (+/- 0.039) liters/kg, respectively. Total urinary excretion of iosulamide represented a mean (+/- SE) of 12.5 (+/- 0.6)% of the administered dose and was virtually complete in 3 hr. The results of the pharmacokinetic study indicate that iosulamide is rapidly cleared from the body and that renal clearance is a minor route of elimination from the body.

Animals↗