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Biomedical subjects

K E Karlsson

Publications and source records attributed to K E Karlsson.

8 recordsLinked to original sources

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

Simultaneous determination of therapeutic plasma concentrations of pethidine and norpethidine in man by electron capture gas chromatography.

An analytical procedure for the simultaneous determination of pethidine and its N-Demethylated metabolite, norpethidine, in plasma is described. Pethidine and norpethidine are separated by partition chromatography, converted to the trichloroethyl carbamate with trichloroethyl chloroformate and determined by electron capture gas chromatography. The smallest amounts of pethidine and norpethidine determined by the method were 10 and 2 ng, respectively, in 0.1 ml plasma. The relative standard deviation in the determination of 50 ng of pethidine and 40 ng of norpethidine in 0.1 ml plasma wwere 5.8% (n = 8) and 6.3% (n = 10), respectively. The method was used to determine plasma levels of pethidine and norpethidine in three patients who received subcutaneous doses of pethidine 50-75 mg for postoperative pain. The peak levels of pethidine were found to be in the range 200-400 ng/ml, with a plasma half-life of the order of 4 hours. The levels of norpethidine were low.

Chromatography, Gas

Determination of pethidine in plasma by electron capture gas chromatography after reaction with trichloroethyl chloroformate.

Pethidine (meperidine) is determined in plasma by electron capture gas chromatography after derivatization with trichloroethyl chloroformate. The analytical procedure involves extraction of pethidine and the internal standard from plasma and their separation from metabolites by partition chromatography. After purification of the eluate, the derivatization is accomplished with trichloroethyl chloroformate in the presence of anhydrous sodium carbonate. The reaction mixture is further purified with methanolic alkali before gas chromatographic analysis. Optimum conditions for extraction and derivatization, as well as the sensitivity and selectivity of the method are discussed. Owing to the high sensitivity the pethidine levels are determined in 0.1 ml of plasma. The smallest amount of pethidine determined by the method was 100 ng/ml. The relative standard deviation at the 50-ng level of pethidine added to 0.1 ml of plasma was 5.8%(n =8).

Buffers

A computer program for an open two compartment system distinguishing three models.

A digital computer program is described for the estimation of parameters in an open two compartment system distinguishing 3 models. The mathematical function to be fitted to a given set of experimental data is given initial estimates for the parameters of the function. The program uses an iterative procedure to adjust the parameters until the sum of squares of residuals has converged to a minimum. Assuming that a given substance is introduced into compartment 1, the function can be fitted to the set of experiment data of that compartment. A set of experimental data from compartment 2 can also be included in the minimizing function. Two optional weighting functions are presented. From the constants of the two-exponential functions the physiological parameters of the three models are determined. Experimental observations of compartment 1 only allow for calculation of physiological parameters of two of the models.

Computers

A metabolic route of omeprazole involving conjugation with glutathione identified in the rat.

A metabolic route of omeprazole involving glutathione has been established through identification of endproducts excreted in the urine of rats after oral administration of 400 mumol/kg of a mixture of [3H]- and [14C]omeprazole. The labeled positions enabled facile tracing of metabolites that were formed through fission of omeprazole, producing [3H]pyridine and [14C]benzimidazole metabolites. The structures of the metabolites were established by HPLC thermospray MS and MS/MS. Two of the metabolites were isolated and characterized by 1H NMR studies. The fact that the N-acetylcysteine derivative of the benzimidazole was one of the endproducts indicated that the initial reaction involved glutathione. Three metabolites reflecting the fate of the pyridine moiety were identified. Their proposed formation route is via initial reduction to the pyridylmethylthiol compound followed by S-methylation and S-oxidation to the corresponding sulfoxide or sulfone. The quantity of metabolites formed via the glutathione route identified in urine was about 10% of the dose given, both in male and female rats. The male and female rats excreted the same cleaved metabolites and approximately equal quantities thereof.

Animals