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C Lindberg

Publications and source records attributed to C Lindberg.

At least 73 records · Page 4Linked to original sources
PubMed1988

Determination of drug enantiomers in biological samples by coupled column liquid chromatography and liquid chromatography-mass spectrometry.

Liquid chromatography-mass spectrometry (LC-MS) and coupled column chromatography can be used to overcome problems likely to occur in direct separation and determination of drug enantiomers in biological samples. This is exemplified here with the direct separation and determination of terbutaline in human plasma at the nmol/l level. A beta-cyclodextrin column with an aqueous mobile phase was used for chiral separation. For coupled column chromatography, the concentration of each enantiomer was calculated from the enantiomeric area ratio and the racemate concentration. A deuterium-labelled internal standard was used in the LC-MS experiments.

Chromatography, Gas↗
PubMed1988

Comparative pharmacokinetics of unlabeled and deuterium-labeled terbutaline: demonstration of a small isotope effect.

An equimolar mixture of terbutaline and [2H6]terbutaline was given as an oral solution to six healthy volunteers (three men and three women). Frequent blood samples were collected during a 24-h period and the plasma concentrations of unlabeled and deuterium-labeled terbutaline were measured by GC-MS. The overall geometric mean plasma concentration ratio of terbutaline to [2H6]terbutaline (isotope ratio) was 1.04 and differed significantly from unity. The difference can be explained by a difference in lipophilicity between the analogues, affecting their absorption. No trend in isotope ratio over the experimental time was observed. For unknown reasons, the isotope ratio was higher for women (1.07) than for men (1.00). Deuterium-labeled terbutaline can be used, intravenously or orally, as an absolute reference in bioavailability studies on terbutaline. If deuterium-labeled terbutaline is given orally in a single-day relative bioavailability study, a correlation should be made for the observed isotope effect.

Adult↗
PubMed1987

The use of on-line liquid chromatography/mass spectrometry and stable isotope techniques for the identification of budesonide metabolites.

A moving belt interface was used to identify budesonide metabolites, obtained from rat and mouse liver incubations, by liquid chromatography/mass spectrometry (LC/MS). The metabolites were separated on a small-bore C18 column with an ethanol/water gradient as mobile phase at a flow rate of 0.2 ml min-1. A spray device was used for deposition of the aqueous solvent on to the belt. Chemical ionization mass spectra were obtained with methane as the reagent gas. Deuterium-labelled budesonide, which was used to facilitate metabolite identification by the isotope cluster technique, was found to be slightly separated from the unlabelled analogue on the LC column. Incubations were also performed under 18O2 to elucidate the mechanism of a new metabolic pathway (16 alpha, 17 alpha-acetal splitting) and to confirm the oxidative nature of reactions leading to hydroxylated metabolites. The moving belt LC/MS technique afforded higher sensitivity, and gave more abundant MH+ ions of the compounds studied, than previously found by direct probe mass spectrometry. Phthalate ester background, partly from the polymide belt, complicated the identification of minor metabolites.

Animals↗
PubMed1984

Acute and temporary inhibition of thymidine kinase in mouse bone marrow cells after low-dose exposure.

Low-dose whole-body exposure of mice to less than 0.01 Gy gamma-rays causes inhibition of incorporation of thymidine or 5-iodo-2-deoxyuridine into DNA of bone-marrow cells in vitro; the effect is maximal in cells at 4 hours after exposure and then subsides within about 10 hours. This is due to the inhibition of cellular thymidine kinase, which gradually develops to a maximum at 4 hours after exposure and again subsides within the next 10 hours. This inhibition involves only 35 per cent of the entire cellular enzyme activity and, analogous to the depression of thymidine incorporation into the cells, is only seen when the cells are collected into medium that is buffered to 7.2-7.4 and contains about 1350 mg NaHCO3 per litre. Addition of NaHCO3 to the cell homogenate or to the high speed supernatant containing the enzyme, but not to intact cells, failed to produce enzyme inhibition. There is also no depression of 5-iodo-2-deoxyuridine uptake into the intact cells in vitro when the mice are irradiated either shortly before or after i.v. injection of 0.02 mg of procain chloride. The reversibility of the effect in vivo and in vitro suggests a particular enzyme control mechanism that may be non-specifically triggered by intracellular charges, such as peroxides, and may enhance repair.

Animals↗
PubMed1984

Kinetics of terbutaline in asthmatic children.

Seven asthmatic children (8-12 years) were given terbutaline sulphate intravenously (5.5 micrograms/kg) and orally (50 micrograms/kg) one week apart. Unchanged terbutaline was measured in plasma and urine. In urine, conjugates were also assayed. The intravenous plasma concentration-time curve declined in a multiexponential manner. The terminal half-life ranged from 8.8 to 15.8 (mean 12.1) h. Body clearance (mean +/- SD) was 3.76 +/- 0.86, renal clearance 2.42 +/- 0.49 mL/min/kg. The volume of distribution at steady state was 1.57 +/- 0.19 L/kg. The extrapolated recovery of intact terbutaline in urine was 65.4 +/- 6.5% of the dose and the total recovery 80.8 +/- 8.4%. After oral administration, the recovery of intact terbutaline in urine was 6.2 +/- 1.1%. Absorption was on average 33%, but because of a mean first-pass elimination of 70%, bioavailability was 9.5 +/- 2.4%. It seems that children as a group have shorter terminal half-lives than adults and slightly higher weight-corrected clearances.

Administration, Oral↗
PubMed1984

Terbutaline in the treatment of preterm labour.

Continuous terbutaline infusion in 8 women with premature labour arrested the uterine contractions within 1.5 h in 7 of them when an infusion rate of 10 micrograms/min was used. The plasma concentrations of terbutaline were in the range 10-14 micrograms/L after 1 h. In 4 other women with less severe contractions, labour could be stopped with infusion rates of 5 or 7.5 micrograms/min. A condition approaching steady state seemed to be attained after infusion at a constant rate of 2.5 micrograms/min for 17-34 h with a mean plasma concentration of 6.7 micrograms/L. This value would give a mean total body clearance of 0.30 L/min which is about one third higher than that previously found in healthy men. The terbutaline plasma concentrations determined in this study were compared with simulated curves based on pharmacokinetic parameters obtained in healthy male volunteers. The data correlated well during the first 3 h of infusion, indicating similar distribution kinetics in the patients and the volunteers. After infusion for a longer period (greater than 10 h), the measured plasma concentrations were generally lower than those predicted by the simulation. Treatment of 10 women (7 initially treated intravenously) with terbutaline tablets 5 mg three times daily postponed delivery for more than 7 days in 9 of the patients. The mean plasma concentrations of terbutaline during repeated tablet treatment were 3.4, 4.1 and 4.1 micrograms/L at 1, 2 and 4 h after administration, respectively. No serious side-effects occurred.

Administration, Oral↗
PubMed1984

Quantitative analysis of terbutaline by gas chromatography-mass spectrometry.

Over the past 6 years, several gas chromatography-mass spectrometry (GC-MS) methods for terbutaline have been developed, each with certain advantages and disadvantages. They all involve monitoring of an ion selected from the mass spectrum of a suitable terbutaline derivative. This technique, often referred to as mass fragmentography or selected ion monitoring, reduces the interference from other drugs and endogenous compounds. Different ionization techniques have been employed to obtain high sensitivity, viz. electron impact and chemical ionization. Typically, the methods can be used to measure terbutaline concentrations down to 0.1-0.3 ng/mL in plasma or serum. Isolation of terbutaline from biological materials is complicated by the low partition of the drug from water to organic solvents. Extraction with a large volume of ethyl acetate, ion pair extraction, or isolation on a cation exchange column have been used. These methods are time consuming, and attempts have therefore been made to modify them. Rapid extraction can be achieved on a disposable reversed-phase octadecylsilyl column with unimpaired sensitivity and selectivity. Preliminary results indicate that negative ion chemical ionization of a fluorine-containing derivative can further increase the sensitivity of the terbutaline assays.

Gas Chromatography-Mass Spectrometry↗
PubMed1984

Pharmacokinetic implications of slow equilibration of terbutaline between plasma and erythrocytes.

The erythrocyte: plasma concentration ratio of terbutaline was measured in 3 healthy volunteers during and after a steady-state dosing interval. The dose regimen was 3 X 5 mg. The ratios varied only moderately with time. Average ratios of 2.0, 2.2 and 2.6 were found in the 3 subjects. The uptake rate of terbutaline into erythrocytes was studied in vitro. Freshly drawn human blood samples had terbutaline added at a concentration of about 3 ng/mL and were then maintained at room temperature and physiological pH and pCO2. The plasma concentration fell and the erythrocyte concentration rose continuously during the following 8 h, the ratio reaching unity after 6 h. Assuming a monoexponential uptake and a final ratio in vitro similar to that in vivo (about 2.3), we would estimate an uptake half-time between 3.5 and 8.5 h. The two optical isomers of terbutaline did not differ in their uptake rates. In vivo data suggest a much faster uptake. Nevertheless, it may be slow enough to affect the kinetics of terbutaline. The fact that the equilibration process continues in vitro in a withdrawn blood sample also calls for rapid separation of plasma from erythrocytes if plasma levels of terbutaline are to be accurately measured.

Diffusion↗
PubMed1984

Transfer of terbutaline into breast milk.

Terbutaline has been determined in milk and plasma from 4 nursing mothers treated with Bricanyl tablets (2.5 or 5 mg, 3 times daily) because of obstructive lung disease. Both doses produced milk concentrations of terbutaline in the range 2.5-4.6 ng/mL, which were similar to or higher than the concentrations found in plasma. The highest milk:plasma concentration ratios (up to 2.9) were observed at the beginning and end of the dosage interval. The infants in this study were estimated to have ingested about 0.4-0.6 micrograms/kg/day of terbutaline base, which corresponds to 0.2-0.7% of the daily dose per kg taken by the mothers. Terbutaline was not detectable in plasma when samples were taken from one of the infants and no symptoms of beta-adrenoceptor stimulation could be found in any of the babies.

Biological Transport↗
PubMed1982

Simultaneous determination of terbutaline and salbutamol in plasma by selected ion monitoring.

We describe a method for simultaneous determination of terbutaline and salbutamol in plasma, based on gas chromatography chemical ionization mass spectrometry. Deuterium labelled terbutaline was used as internal standard for both drugs. The method has been used for the analysis of plasma samples obtained from asthmatic patients. The coefficient of variation at 0.3 ng ml-1 was 4.6% for terbutaline and 5.3% for salbutamol with a sample volume of 4 ml. The recovery of both drugs was greater than 80%.

Albuterol↗
PubMed1982

Radioimmunoassay and chemical ionization/mass spectrometry compared for plasma cortisol determination.

We describe a method for determination of cortisol in plasma and urine, based on chemical ionization/mass spectrometry with deuterium-labeled cortisol as the internal standard. The within-run precision (CV) was 2.5-5.7%, the between-run precision 4.6%. Results by this method were compared with those by a radioimmunological method (RIANEN Cortisol, New England Nuclear) for 395 plasma samples. The latter method gave significantly higher (approx. 25%) cortisol values.

Administration, Topical↗
PubMed1981

Single injection of terbutaline in term labor: placental transfer and effects on maternal and fetal carbohydrate metabolism.

Maternal and fetal blood glucose and insulin levels were studied in 10 women in the second stage of labor after administration of terbutaline, 250 micrograms intravenously. The transport of the drug across the placenta was also studied. Saline solution was administered to four other women who served as controls. A rise in maternal plasma insulin levels occurred in all patients but was more pronounced in patients treated with terbutaline less than 25 minutes before delivery than in those treated more than 45 minutes prior to delivery. No difference was found in maternal blood glucose levels between terbutaline-treated patients and controls. Blood glucose increased in the fetuses during the second stage of labor and paralleled that of the mothers, but on a lower level. None of the newborn infants demonstrated hypoglycemia during the first 90 minutes after birth. Terbutaline crossed the placenta rapidly, and fetal plasma levels up to 55% of the maternal plasma levels were found. The conclusion is that this form of administration of terbutaline does not seem to have any negative short-term influences on the fetal carbohydrate metabolism.

Blood Glucose↗
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

Determination of terbutaline in plasma by gas chromatography chemical ionization mass spectrometry.

A method is described for the determination of unconjugated terbutaline in plasma. The assay is based on gas chromatography chemical ionization mass spectrometry with ammonia as the reagent gas. Terbutaline and a deuterium labelled internal standard were isolated from plasma by ion exchange chromatography followed by extraction into t-butanol. Quantitation was performed by selected ion monitoring of the [MH]+ions m/z 442 and m/z 448 of the tri-O-TMS derivatives of terbutaline and the internal standard, respectively. Silylation was carried out in the presence of pyridine at room temperature and was complete within one minute. The overall recovery of terbutaline in the procedure was estimated at about 80%. Measurement of terbutaline down to 0.1 ng ml-1 in 4 ml of plasma is possible with a coefficient of variation of 8.6%. Day-to-day variation was found to be 6.0% at a level of 3.26 ng ml-1.

Gas Chromatography-Mass Spectrometry↗
PubMed1978

A selected ion monitoring method for the determination of pethidine and norpethidine in plasma. Comparison with a gas chromatographic method using electron capture detection.

An analytical procedure for the simultaneous determination of pethidine and norpethidine in plasma by selected ion monitoring is described. The method has a capacity of 15--20 analyses per hour and can be used to determine pethidine and norpethidine down to 25 ng ml(-1) and 5 ng ml(-1), respectively. The selected ion monitoring method has been compared with a method based on electron capture detection after analysis of pethidine and norpethidine in spiked plasma samples and in plasma from patients. The two methods are capable of performing selective and accurate determinations of pethidine and norpethidine, in the concentration ranges obtained in man after a single therapeutic dose of pethidine.

Chromatography, Gas↗