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J Taskinen

Publications and source records attributed to J Taskinen.

At least 55 records · Page 3Linked to original sources
PubMed1991

Determination of a catechol-O-methyltransferase inhibitor, nitecapone, in human plasma and urine by liquid chromatography.

Methods based on reversed-phase liquid chromatography with amperometric detection have been developed for determination of nitecapone, 3-(3,4-dihydroxy-5-nitrobenzylidene)-2,4-pentanedione, a COMT inhibitor, in human plasma and urine. Nitecapone was extracted with ethyl acetate-hexane mixtures from plasma after acidification with hydrochloric acid and from urine as the tetrabutylammonium ion-pair of its diphenylborate derivative. The recoveries of both methods exceeded 70% and the relative standard deviations for within-day precision were less than 4% and 8% at 50 ng ml-1 and at the quantitation limits, respectively. The methods are selective, sensitive and precise enough for determination of 4-5 ng ml-1 of nitecapone in plasma and urine and are thus suitable for the kind of pharmacokinetic studies exemplified in this paper.

Calibration↗
PubMed1988

Hydrolysis of 2'-esters of erythromycin.

Hydrolysis rates were determined for 2'-acetyl erythromycin, three of its homologues (2'-propionyl, 2'-butyryl and 2'-valeryl) and 2'-ethylsuccinyl erythromycin in buffer solution (pH 7.0, 37 degrees C) and in human plasma (37 degrees C) at concentrations of 5 and 100 mg/l. Ester concentrations were measured by fast atom bombardment mass spectrometry. Hydrolysis in buffer followed pseudo first-order kinetics. The half-lives of the esters ranged from 24.3 to 89.5 min (2'-ethyl-succinyl less than 2'-acetyl less than 2'-propionyl less than 2'-valeryl less than 2'-butyryl). Hydrolysis in plasma followed more complex kinetics. The half-lives were generally longer than in buffer and dependent on the initial ester concentration. Apparent first-order half-lives ranged from 35.5 to 492 min (2'-ethylsuccinyl less than 2'-acetyl less than 2'-propionyl less than 2'-butyryl less than 2'-valeryl). In case of homologous esters, the stabilizing effect of plasma and concentration dependence varied with lipophilicity. In buffer solution the hydrolysis half-life of 2'-acetyl erythromycin was dependent on the concentration of alpha 1-acid glycoprotein. Of the homologous esters, 2'-acetyl erythromycin was hydrolysed most rapidly, but it was hydrolysed more slowly than 2'-ethylsuccinyl erythromycin.

Animals↗
PubMed1988

Fate of single oral doses of erythromycin acistrate, erythromycin stearate and pelleted erythromycin base analysed by mass-spectrometry in plasma of healthy human volunteers.

The kinetics of erythromycin acistrate (EA). a new ester prodrug of erythromycin, were studied in three comparative, randomized, cross-over studies in 29 healthy volunteers. A new mass-spectrometric method was used to assay separately erythromycin, 2'-acetyl erythromycin and their anhydro (spiroketal) forms. In Part I, the total antibiotic concentration was higher after EA than after erythromycin stearate (ES; 1.8-fold) and enterocoated pellets of erythromycin base (EB, enterocapsules; 1.4-fold). In plasma, however, only about one third of 2'-acetyl erythromycin was hydrolysed to active erythromycin. Moreover, after unprotected EA tablets, a considerable proportion of erythromycin and 2'-acetyl erythromycin was inactivated by gastric acid as reflected by high concentrations of respective anhydro (spiroketal) forms. In Part II, the unprotected (regular tablets) and acid-protected tablets (dissolution starts at pH 4.5) were compared. The protected tablet, albeit not an enterotablet, was not destroyed by gastric acid. Its absorption was slightly delayed but the bioavailability was good. In this study, the absorption of total antibiotic was 2.8-fold (unprotected tablet) and 3.9-fold (protected tablet) that after enterocapsules. In Part III, the bioavailabilities of 200 and 400 mg tablets (both acid-protected) were equal.

Administration, Oral↗
PubMed1987

Quantitative determination of erythromycin 2'-ethylsuccinate in human plasma by fast atom bombardment mass spectrometry.

A method for simultaneous quantitative determination of erythromycin 2'-ethylsuccinate and erythromycin in human plasma is described. After extracting the deuterium-labelled internal standards and analytes from alkalinized plasma to diethyl ether the extracts were analysed by fast atom bombardment mass spectrometry. The quantification limit for 2'-ethylsuccinate ester was 50 ng ml-1 and for erythromycin 100 ng ml-1. The calibration curves were linear up to 5 micrograms ml-1 for both. The precision of the method at higher concentration was less than 2% and at the quantification limit approximately 6% for both analytes.

Deuterium↗
PubMed1985

Assessment of bioavailability of experimental single-unit sustained release tablets of verapamil hydrochloride using the stable isotope technique.

A stable isotope technique has been used to assess the bioavailability of sustained release verapamil products. The test formulations were tablets with a core containing 90 mg of verapamil hydrochloride coated with ethylcellulose film, the permeability of which was controlled using different amounts of hydroxypropyl methylcellulose. A product containing ethylcellulose 75% hydroxypropyl methylcellulose 25% w/w gave a single-unit sustained release tablet of verapamil hydrochloride that allowed a dose interval of 24 h. There was no loss in bioavailability, even though verapamil had extensive first-pass metabolism.

Absorption↗
PubMed1982

Quantitative determination of nitroglycerin in human plasma by capillary gas chromatography negative ion chemical ionization mass spectrometry.

A quantitative method for determination of nitroglycerin in human plasma was developed. Nitroglycerin and the internal standard (butane-1,2,4-triyl trinitrate) were extracted from plasma with pentane. The extracts were analysed by gas chromatography mass spectrometry using fused silica capillary columns and electron capture negative ion chemical ionization. The quantitation limit of the method was about 50 pg ml-1. Linear calibration curves were obtained in the range of 50-1600 pg ml-1. Precision at the level of 100 pg ml-1 was 4%.

Administration, Topical↗
PubMed1981

Trioxsalen bath plus UVA treatment of psoriasis. Plasma concentration of the drug and clinical results.

Forty-five patients with psoriasis were treated with trioxsalen bath plus UVA. Good or excellent results were obtained in 34 (67%) of the 51 treatments. Trioxsalen plasma concentrations were determined at different stages of the treatment in 10 patients 1 hour after trioxsalen bath, and in 11 patients undergoing treatment for vitiligo 2 hours after ingestion of 0.6 mg trioxsalen per kilogram body weight. The determinations were performed using the glass capillary, gas chromatography, mass spectrometry method, reaching a sensitivity of greater than or equal to 25 pg/ml. The trioxsalen plasma concentrations varied between 12.5 and 0.27 ng/ml after oral ingestion and between approximately 9 ng/ml and less than 25 pg/ml after bath application.

Adolescent↗
PubMed1980

Determination of trioxsalen in human plasma in the picogram range by glass capillary gas chromatography mass spectrometry.

Two methods based on glass capillary gas chromatography mass spectrometry have been developed for quantitative determination of trioxsalen, a photosensitizing drug, in human plasma. One employs the extraction of trioxsalen and deuterated internal standard from plasma with dichloromethane and purification of the extract by high pressure liquid chromatography before analysis by selected ion monitoring at low resolution. In the other procedure the raw hexane extracts are analysed by selected ion monitoring at medium resolution. Both methods can be used to determine trioxsalen over the range 25 pg ml-1 to 2 ng ml-1, which corresponds to the range of plasma concentration present after application of trioxsalen as bath.

Chromatography, Liquid↗
PubMed1978

Pharmacokinetics and side-effects of clonidine.

A single oral dose of clonidine 300 microgram was administered to 8 healthy, normotensive subjects and the time course of its plasma concentrations was followed for 24 h. The plasma concentration of clonidine rose to a peak of 1.17 +/- 0.12 ng/ml at about 2 h: the absorption half-life was 0.6 +/- 0.2 h. Elimination followed first order kinetics with a half-life of 7.7 +/- 2.0 h. The correlation between the two most common side-effects of clonidine, sedation and dryness of the mouth, with the time course of its plasma concentrations was highly significant, p less than 0.01. All the subjects complained of severe sedation. During continuous administration of clonidine (75 microgram t.i.d.) for one week a steady state serum level of 0.30-0.35 ng/ml was achieved. One 75 microgram tablet of clonidine raised the serum level to about 0.69 +/- 0.13 ng/ml in two hours. After cessation of dosing, the serum level declined with a half-life of 7.5 +/- 1.5 h. The urinary excretion of unchanged clonidine was found to be about one third of the administered dose in 24 h during continuous administration and in the first 24 h after the single oral dose.

Adult↗
PubMed1975

Chemical composition of angelica root oil.

The volatile constituents of angelica root separated by extraction with etherpentane and by extraction with alcohol-water were investigated by means of glass capillary and preparative gas chromatography, IR, UV, NMR and mass spectrometry. 16 monoterpene hydrocarbons, 13 sesquiterpene hydrocarbons, 12 monoterpene alcohols, 4 oxygenated sesquiterpenes, 11 esters, 3 lactones, 7 aliphatic carbonyl compounds and 4 aromatics were identified. Twenty additional compounds identified were present only in the alcoholic sample. These consisted of ethyl ethers of monoterpene alcohols, ethyl esters of long-chain fatty acids, and acetals. The relative proportion of many compounds was found to depend on the method used to isolate the essential oil.

Chromatography, Gas↗
PubMedDate not supplied

Pharmacokinetics of sustained-release verapamil after a single administration and at steady state.

Pharmacokinetics of conventional 80 mg tablets and two types of sustained-release (SR) tablets containing 120 and 200 mg of verapamil were compared cross-over in 12 healthy volunteers. Serum concentrations of verapamil and norverapamil were analyzed both after a single oral dose and at steady state after t.i.d. administration of conventional tablets and b.i.d. administration of SR tablets. After 120 mg SR tablets serum concentrations of verapamil usually remained below 100 ng/ml for 5 days. This inadequate bioavailability was caused by very slow absorption. The relative bioavailability of verapamil in 200 mg SR tablets was 93-96% as compared to the conventional tablets. After 200 mg X 2 and 80 mg X 3, the peak serum levels were about 300 and 190 ng/ml, respectively and the trough levels 123-153 and 52-56 ng/ml, respectively. The verapamil/norverapamil ratio varied from 0.69 to 0.84 after a single dose and from 0.8 to 0.93 at steady-state. By the 4th days of treatment, the accumulation ratios ranged between 1.75-2.07 and 1.30-1.75 for verapamil and norverapamil, respectively. For each preparation studied, the apparent Cltot of verapamil was significantly reduced at steady-state. These results show that 200 mg SR verapamil tablets fulfill the basic requirements of retard preparations allowing for twice or even once daily administration.

Adult↗
PubMedDate not supplied

Identification of major urinary metabolites of the catechol-O-methyltransferase inhibitor entacapone in the dog.

Metabolites of entacapone, (E)-2-cyano-N,N-diethyl-3-(3,4-dihydroxy-5-nitrophenyl) propenamide, a potent inhibitor of catechol-O-methyltransferase, were isolated from dog urine. After hydrolysis of glucuronides and sulfates, 5 metabolites were identified in addition to unchanged entacapone by HPLC with diode-array UV detection, electron ionization mass spectrometry and IR spectroscopy. The (Z)-isomer of entacapone was the most abundant phase I metabolite while less abundant metabolites were formed through cleavage or reduction of the side chain carbon-carbon double bond, hydrolysis of the amide bond or through hydration of the nitrile group. The most abundant urinary metabolites were glucuronides. The glucuronidation site of these ortho-nitrocatechols was shown to be the hydroxyl meta to the nitro group.

Animals↗
PubMedDate not supplied

Enzyme-assisted synthesis and structural characterization of nitrocatechol glucuronides.

Enzyme-assisted synthesis and characterization are described for 3-O-beta-D-glucuronides 1b-4b of the aglycons E- and Z-2-cyano-N, N-diethyl-3-(3,4-dihydroxy-5-nitrophenyl)propenamide (entacapone), 1a and 2a, respectively, 3-(3,4-dihydroxy-5-nitrobenzylidene)-2, 4-pentanedione (nitecapone) 3a and 4'-methyl-3, 4-dihydroxy-5-nitrobenzophenone (tolcapone) 4a, and 1-o- and 2-o-glucuronides 5b and 6b of the aglycon 1, 2-dihydroxy-4-nitrobenzene 5a. Liver microsomes from rats pretreated with Aroclor 1254 were used as catalyst in the synthesis. Glucuronidation was regio- and stereoselective in the case of 1a-4a; only one product was observed by HPLC, HPTLC, and NMR. The glucuronidation of 1,2-dihydroxy-4-nitrobenzene 5a resulted in equal amounts of 1-O-beta-D- and 2-O-beta-D-glucuronides. Purification of the crude products by C18 solid-phase extraction and/or flash chromatography gave compounds 1b-6b in 38-98% yields (50-84 mg). The structures of the glucuronides were characterized on the basis of UV and IR spectra and confirmed with FAB-MS and NMR spectroscopy.

Animals↗