Search PubMed⌕ Search

Biomedical subjects

P Hartvig

Publications and source records attributed to P Hartvig.

At least 199 records · Page 11Linked to original sources
PubMed1980

Electron-capture gas chromatography of plasma sulphonylureas after extractive methylation.

Conditions for the extractive alkylation of eight sulphonylurea hypoglycemic drugs have been evaluated. Extractive methylation of the compounds was achieved within 90 min using tetrabutylammonium as counter-ion (0.1 M at pH = 6.9) with 5% methyl iodide in dichloro-methane as organic phase. Mass spectral analysis showed derivatives methylated at the sulphonamide nitrogen. A higher pH or use of tetrapentylammonium as counter-ion caused hydrolysis of the sulphonylureas. The derivatives showed a high electron-capture response with minimum concentrations detectable in the range 1-4 x 10(-16) moles sec-1. Therapeutic plasma concentrations of glipzide and tolbutamide were determined by direct extractive methylation of the compounds from the plasma sample. The glipizide derivative was determined by electron-capture gas chromatography down to about 20 ng/ml in a 0.5-ml plasma sample. The relative standard deviation at the 0.2 microgram/ml level of glipizide was 6% (n = 6). The corresponding figure in the determination of tolbutamide at the 10 microgram/ml level was 3% (n = 10).

Chromatography, Gas↗
PubMed1980

Investigation of the Urinary excretion of pethidine and five of its metabolites in man using selected ion monitoring.

The urinary excretion in man of pethidine and five of its metabolites (norpethidine, pethidinic acid, norpethidinic acid, p-hydroxypethidine and pethidine N-oxide) after a single intramuscular dose has been investigated using analytical procedures based on selected ion monitoring. New methods for the determination of p-hydroxypethidine and pethidine N-oxide have been developed, and the selectivity and sensitivity of the procedures are discussed. Only some 5% of the administered dose was excreted as unchanged pethidine. The mean urinary excretion of norpethidine was 16.4%. Pethidinic acid and norpethidinic acid constituted the major fraction of the dose excreted in urine. The total excretion of pethidinic acid and norpethidinic acid was 41.7 and 23.2%, respectively. Pethidine N-oxide constituted less than 0.5% of the excreted amount, and p-hydroxypethidine could only be detected in the urine of two of the patients. A mean total recovery of about 90% of the dose was found in urine as pethidine and the five metabolites.

Adult↗
PubMed1980

Clinical pharmacokinetics and oral bioavailability of ketobemidone.

The basic pharmacokinetics and oral bioavailability of ketobenmidone have been studied in 6 patients after surgery. Plasma concentrations were first determined following intravenous administration of Ketogin 2 ml, containing ketobemidone chloride 10 mg and the spasmolytic N,N-dimethyl-3,3-diphenyl-1-methylallylamine chloride 50 mg, and then, on the second postoperative day, following oral administration of 2 tablets of Ketogin, each containing ketobemidone chloride 5 mg and the spasmolytic agent 25 mg. The average oral bioavailability of ketobemiodone was 34% +/- 16% (SD, n = 6). The mean plasma half-life of elimination (t1/2 beta) was about the same following oral (2.45 +/- 0.73 h; SD, n = 5) as after intravenous administration (2.25 +/- 0.35 h; SD, n = 6). The low oral bioavailability and rapid elimination of ketobemidone demonstrated in this study suggest that the usual dosage recommendation for oral Ketogin (ketobemidone 5--10 mg every 6--7 h) in patients with severe pain is too low.

Administration, Oral↗
PubMed1980

Quantitation of CSF concentrations and biological activity of probenecid metabolites.

The concentrations of probenecid and four of its metabolites have been examined in plasma and CSF by electron capture gas chromatography after extractive methylation. The plasma concentration of each of the metabolites was in the range 1,5-15 micrograms/ml and constituted less than 10% of the parent compound. The penetration into CSF of the metabolites was lower than that of probenecid. The concentration of each of the metabolites was below 0,2 microgram/ml and the total concentration never exceeded 10% of the probenecid concentration. The inhibitory effect of the metabolites on uptake was tested in rabbit renal cortex using 3H-p-amino-hippuric acid. The inhibitory effect was low. From the low activity and relatively low concentrations of the metabolites do not contribute to the probenecid-induced blocking effect of acid transport from the CSF.

Animals↗
PubMed1980

Pharmacokinetics and oral bioavailability of pyridostigmine in man.

The pharmacokinetics of pyridostigmine was evaluated after intravenous injection in two healthy male volunteers and after oral administration to five subjects. Plasma concentrations of pyridostigmine were determined after ion pair extraction from plasma and analysis by gas chromatography - mass spectrometry with chemical ionization, using d6-pyridostigmine as internal standard. Degradation of pyridostigmine in vitro was compensated for by use of the deuterated internal standard and by rapid cooling and separation of plasma after blood sampling. After intravenous administration of pyridostigmine 2.5 mg the plasma elimination half-life was 1.52 h, the volume of distribution was 1.43 l/kg and the plasma clearance 0.65 l/kg x h. The pharmacokinetic constants were very similar after oral administration of pyridostigmine 120 mg; the elimination half-life was 1.78 +/- 0.24 h, the volume of distribution 1.64 +/- 0.29 l/kg and the plasma clearance was 0.66 +/- 0.22 l/kg x h. The bioavailability was calculated to be 7.6 +/- 2.4%. When pyridostigmine was taken together with food, the time to reach the peak plasma concentration was prolonged from 1.7 to 3.2 h. Bioavailability, however, was not influenced by concomitant food intake. "Steady-state" plasma concentrations of pyridostigmine were measured in myasthenic patients on their ordinary dose schedule of cholinesterase inhibitor drugs. More than a seven-fold difference in steady-state plasma concentration was found between patients taking approximately the same daily dose of pyridostigmine.

Administration, Oral↗
PubMed1980

Plasma concentrations after bath treatment and oral administration of trioxsalen.

An analytical method comprising homogenous extraction and determination by gas chromatography mass spectrometry has been developed for the quantitation of trioxsalen in plasma. The limit of sensitivity of the method has been 2 ng/ml of trioxsalen. The method was used to monitor concentrations of trioxsalen in plasma after a 40 mg oral dose or after trioxsalen bath treatment. The concentrations in plasma after oral administration did not exceed 3 ng/ml, while in 2 patients after bath treatment trioxsalen could be determined (2-3 ng/ml). The low plasma concentrations found throw light on the poor UV-sensitizing properties found after oral trioxsalen therapy.

Administration, Oral↗
PubMed1980

Quantitation of a bisacodyl metabolite in urine for the diagnosis of laxative abuse.

A 2 year history of severe diarrhea, tiredness, and weight loss in a female patient could not be diagnosed satisfactorily despite repeated and extensive clinical investigations of various kinds. The final diagnosis of laxative abuse was arrived at after identification and quantitation of a bisacodyl metabolite in the urine from the patient. The metabolite was bisacodyl disphenol. The analytical method developed was based on liquid chromatographic determination after hydrolysis of the conjugated metabolite of bisacodyl and selective isolation from the urine. The precision of the method was 5% at the 2.3 microgram/ml level (n = 9) of bisacodyl diphenol, and the absolute recovery was estimated at 80%. The method allowed detection of 0.5 migrogram/ml of the metabolite in urine. After a single dose (10 mg) of bisacodyl to volunteers, urinary concentrations of the metabolite in the range of 1--5 microgram/ml were found. The bisacodyl diphenol recovered in the urine corresponded to 20--30% of the original dose. The urinary concentration of the diphenol derivative in the patient was estimated at 17 microgram/ml.

Adult↗
PubMed1979

Analysis of nicotine as a trichloroethyl carbamate by gas chromatography with electron-capture detection.

Nicotine was subjected to reaction at 90 degrees with trichloroethyl chloroformate in the presence of pyridine to form a carbamate in which the pyrrolidine ring was opened. Upon heat treatment, this carbamate partially formed the corresponding olefin. About 10 pg could be detected with an electron-capture detector and 60 pg with an alkali flame-ionization detector. The extraction was studied with 14C-labelled nicotine. Methylene chloride was suitable for extraction from diluted plasma, whereas toluene containing 5% of heptafluorobutanol was used in a re-extraction step and also as the chloroformate reaction medium. Due to a nicotine blank the limit for quantitative determinations was 10 ng/ml in plasma (sample volume 1 ml). N-n-Propylnornicotine was used as an internal standard. The precision at the 30 ng/ml level was +/- 8.8% (n = 7).

Animals↗
PubMed1979

Extractive alkylation of sulphonamide diuretics and their determination by electron-capture gas chromatography.

The extractive alkylation of 11 sulphonamide diuretics has been evaluated using tetrabutylammonium, tetrapentylammonium or tetrahexylammonium as counter ion at different pH values and methyl iodide in methylene chloride as the organic phase. The sulphonamides are methylated within 20 min with tetrahexylammonium as counter ion in 0.2 M sodium hydroxide at 50 degrees. The derivatives have been identified by mass spectral and nuclear magnetic resonance analysis. Relative retentions of the derivatives are given using 1% SE-30 as the stationary phase. A contaminant, dimethylsulphuric acid, occurs in methyl iodide and seriously disturbs the gas chromatographic analysis. The application of the extrative alkylation to biological samples is demonstrated by the direct analysis of acetazolamide in serum. 0.1 M tetrapentylammonium in 0.5 M sodium hydroxide is suitable as the aqueous phase with 1.6 M methyl iodide as alkylating reagent in methylene chloride. The trimethyl derivative of acetazolamide formed has been determined by electron-capture gas chromatography down to 0.5 microgram/ml in a 0.1-ml serum sample. The relative standard deviation at the 10 microgram/ml level is 6.6% (n = 10).

Acetazolamide↗
PubMed1979

Patient controlled analgesic therapy in the early postoperative period.

Fourteen patients with postoperative pain were allowed to self-administer preset doses of pethidine intravenously via a logic-controlled motor syringe. Plasma samples were collected during anaesthesia and the postoperative self-administration period, and the concentrations of pethidine and nor-pethidine were determined. Separate single-dose studies in eight patients yielded pharmacokinetic parameters which made possible computer simulations of continuous plasma concentration curves for the anaesthesia and postoperative self-administration period. The consumption of pethidine showed great interindividual variations with a mean consumption for the entire group of 26 mg per hour. The patients established steady-state plasma concentrations with far less than the maximum amount of pethidine allowed. The mean measured plasma concentration of pethidine which provided adequate analgesia was 738 +/- 149 ng/ml. Simulated and measured plasma concentrations were in close agreement. The individual mean drug consumption per hour during self-administration correlated closely with the individual elimination rate of pethidine. No serious side effects were observed. Thus, patient-controlled analgesic therapy offers an individualized analgesic supply to meet an analgesic demand which is governed by each patient's appreciation of pain.

Adult↗