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I Zolle

Publications and source records attributed to I Zolle.

At least 19 recordsLinked to original sources
PubMed1997

Simultaneous analysis of 2-methoxyphenylmetyrapone and its seven potential metabolites by high-performance liquid chromatography.

A sensitive and specific high-performance liquid chromatographic (HPLC) assay has been developed for the quantification of 2-methoxyphenylmetyrapone (2-MPMP) and its seven potential metabolites in rat urine and whole blood. 2-MPMP, 2-hydroxyphenylmetyrapone and their N-oxides, together with 2-methoxyphenylmetyrapol, 2-hydroxyphenylmetyrapol and their N-oxides were separated on an Isco Spherisorb ODS-2 reversed-phase column (250 x 4.6 mm, I.D., 5 microm), with an Isco Spherisorb ODS-2 guard cartridge (10 x 4.6 mm I.D.). A gradient elution was employed using solvent system A (acetonitrile-water-triethylamine-acetic acid, 27.3:69.1:0.9:2.7%, v/v) and solvent system B (methanol), the gradient program being as follows: initial 0-4 min A:B=74:26; 4-10 min linear change to A:B=50:50; 10-16 min maintain A:B=50:50; 16 min return to initial conditions (A:B=74:26). Flow-rate was maintained at 1.25 ml/min, and the eluent monitored using a diode array multiple wavelength UV detector set at 260 nm. Most of the analytes were baseline resolved, and analysis of samples recovered from blood or urine (pH 12, 3 x 5 ml of dichloromethane, recovery approximately 20-95%) revealed no interference from any co-extracted endogenous compounds in the biological matrices, except for 2-hydroxyphenylmetyrapol N-oxide (2-OHPMPOL-NO) at low concentrations. The calibrations (n=6) were linear (r > or = 0.996) for all analytes (approximately 0.5-100 microg/ml), with acceptable inter- and intra-day variability. Subsequent validation of the assay revealed acceptable precision, as measured by coefficient of variation (C.V.) at the low (0.5 mg/ml), medium (50 microg/ml) and high (100 microg/ml) concentrations. The limits of detection for 2-MPMP and their available potential metabolites, except 2-OHPMPOL-NO, in rat urine and blood were both 0.5 microg/ml, respectively.

Animals↗
PubMed1997

Spectral and chromatographic properties of 2-methoxyphenylmetyrapone and its potential metabolites.

In the search for new metyrapone derivatives as radioligands for the functional diagnosis of adrenal pathology, 2-methoxyphenylmetyrapone [2-MPMP, 1-(2-methoxyphenyl)-2-methyl-2-(3-pyridyl)-1-propanone] (1), and related 2-substituted phenylmetyrapone derivatives, have been separated as potent inhibitors of adrenal 11 beta-hydroxylase, with high affinity for adrenal mitochondrial binding sites. Surprisingly, 2-[11C]MPMP showed a rapid loss of the radioactive label, which prompted investigation of its metabolism. Synthetic 2-MPMP (1) and its seven potential metabolites (2-8) have been identified spectroscopically (1H- and 13C-NMR and mass spectrometry) and further characterised by chromatography (TLC and gradient reversed-phase HPLC). Chromatographic and mass analysis of urinary extracts from rats dosed with 2-MPMP have confirmed the major metabolites as 2-hydroxyphenylmetyrapone (2-OHPMP), 2) and its N-oxide (2-OHPMP-NO, 6), which are present predominantly as conjugates.

Animals↗
PubMed1996

Urinary metabolic profile in rat of 1-(2-methoxyphenyl)-2-methyl-2-(3-pyridyl)-1-propanone: a potential radioligand for functional diagnosis of adrenal pathology.

1. The metabolism of 1-(2-methoxyphenyl)-2-methyl-2-(3-pyridyl)-1-propanone (2-MPMP) was studied in the male Sprague-Dawley rat after 50 mg/kg, i.v. dose. 2. Organic solvent extracts of urine samples were directly analysed by reversed-phase gradient hplc. The identified metabolites were also isolated by preparative tlc, and analyzed by direct probe mass spectrometry. In the case of conjugated metabolites, the urine samples were deconjugated by enzyme hydrolysis prior to extraction. The structures of metabolites were confirmed by comparison of their chromatographic behaviours, UV spectra, and mass spectra with those of authentic standards. 3. The metabolites identified in the 0-24-h urine samples were 2-hydroxyphenyl-metyrapone (2-OHPMP) and 2-hydroyphenylmetyrapone N-oxide (2-OHPMP-NO), which were present predominantly as their glucuronide and/or sulphate conjugates. 4. 2-MPMP and four of its metabolites present in the 0-24-h urine samples were quantified by a reversed-phase hplc method. The mean total urinary excretion was 75.4% of the administered dose. The major metabolites present in the urine were conjugates of 2-OHPMP-NO (54.4%) and of 2-OHPMP (18.6%). The excretion of the unchanged drug, unconjugated 2-OHPMP and 2-OHPMP-NO accounted for 1.1, 1.1 and 0.2% of the dose respectively.

Adrenal Gland Diseases↗
PubMed1995

Synthesis of 2-[131I]iodophenyl-metyrapone using Cu(I)-assisted nucleophilic exchange labelling: study of the reaction conditions.

2-Bromophenyl-metyrapone has been synthesized as a precursor for Cu(I)-assisted labelling with radioiodine. A labelling yield of > 95% was obtained and the specific activity of the purified product was 120 GBq/mumol. The iodo for bromo exchange requires an excess of reducing agents to maintain the Cu(I) redox potential. The effects of the amount of reactants, temperature and time were studied. The labelling yield showed a direct dependence on the amount of precursor and Cu(+)-catalyst used for the reaction, and an increase with reaction time (optimal at 60 min) and temperature (optimal at 100 degrees C). Studies of the stability, lipophilicity and binding of 2-[131I]iodophenyl-metyrapone to serum protein indicated high in vitro stability, high lipophilicity (log P = 2.19) and a loose association with serum proteins.

Animals↗
PubMed1985

Dry aerosol of monodisperse millimicrospheres for ventilation imaging: production, delivery system, and clinical results in comparison with 81m-krypton and 127-xenon.

The production of monodisperse human albumin millimicrospheres (diameter less than 1 micron) and labeling with 99mTc is described. A system constructed to nebulize and deliver a dry aerosol yielded a lung delivery efficiency of approximately 25%. In 48 patients without and with varying degrees of chronic obstructive lung disease, quantitative comparison with 81mKr (penetration index, regional distribution of activity in the lungs) demonstrated similar penetration of the particles to the lung periphery (r = 0.89 and r = 0.94, respectively). Qualitative comparison with 81mKr or 127Xe showed complete or a high degree of diagnostic agreement in all but one patient. Semiquantitative scoring of hot spots as a substrate of local turbulent airflow showed a close inverse correlation (r = -0.82) with the forced expiratory volume in 1 s (FEV 1.0%), thus providing additional information about the severity of the airway obstruction. In 24 patients with suspected pulmonary embolism, complete agreement between aerosol and 81mKr images was found in all patients studied. For same-day ventilation/perfusion studies, labeling of the millimicrospheres with 111In yielded images of comparable quality to those obtained with the 99mTc-labeled aerosol.

Aerosols↗
PubMed1983

Synthesis of radioiodinated metyrapone--a potential adrenal imaging agent.

Metyrapone has been labelled with radioiodine selectively in the 4'-position of ring B. The synthesis of 123I-(131)-metyrapone involves four intermediate compounds. 4'-Bromo-metyrapone serves as a stable precursor that is labelled before use. Studies of the biodistribution of [131I]metyrapone in rats indicate the highest concentration in the adrenal gland 10 min after the injection with a fast elimination of the radioactivity. However, the absolute uptake in the normal adrenal is low. When [123I]metyrapone was used in a patient with bilateral hyperplasia, faint adrenal images were obtained.

Adrenal Glands↗
PubMed1978

Uptake by blood components and by subcellular platelet fractions of 1-14C-acetylsalicylic acid.

1-14C-Acetylsalicylic acid was used to study the distribution and the kinetics of the acetyl group in blood components. Tests were carried out in 4 patients in vivo and on four blood samples in vitro. At various intervals after tagging, whole blood, plasma, platelets and platelet fractions were examined. In vitro, relative activity was found to be higher in platelets than in all other blood components. When platelet fractions were examined, the highest specific activity was found in membranes. In vivo, rapid disappearance of activity from circulation was observed. The decrease of activity was slower in platelets than in whole blood and in plasma. The highest specific acitivty was again found in platelet membranes. The half-life of the 14C tag was measured in all components. It was found to be longest in platelet membranes where it corresponded to the half-life of platelets in circulation. From the results obtained, the conclusion was drawn that irreversible acetylation of the platelet membrane must be considered to be one of the main causes of platelet dysfunction induced by acetylsalicylic acid.

Aspirin↗