[Toxicologic analysis of some adrenergic-beta blockers in the diagnosis of intoxications]. / Analiza toksykologiczna wybranych beta-adrenolityków w diagnostyce zatruc.

The study aimed at finding effective techniques of qualitative and quantitative analysis of selected beta-adrenergic blockers, useful both for monitoring of therapy and for thanatological diagnosis of intoxications. The studies took advantage of gas chromatography (GLC) and high performance liquid chromatography (HPLC). For isolation of studied compounds from biological material, classical and solid phase extraction procedures (SPE) Extrelut-20 (Merck), Abselut Nexus (Varian), STRATA C--18 E (Phenomenex) were used. The program included the analysis of most frequently applied derivatives: Acebutolol, Atenolol, Bunitrolol, Bupranolol, Labetolol, Metipranolol, Metoprolol, Oxprenolol, Practolol, Propranolol.

Determination of some cardiovascular drugs in serum and urine by capillary isotachophoresis.

The separation and determination of amiloride, metoprolol, deacetylmetipranolol, labetalol and furosemide in human serum and urine by capillary isotachophoresis were investigated. Amiloride and beta-blockers were separated by cationic isotachophoresis in the electrolyte system sodium morpholinoethanesulfonate buffer (pH 5.5) (cL = 10 mM)-glutamic acid. Furosemide was separated using the anionic electrolyte system histidine hydrochloride buffer (pH 6.2) (cL = 10 mM)-morpholinopropanesulfonic acid. Endogenous and the possible exogenous compounds were almost totally removed from serum and urine by solid-phase extraction using a Separon SGX C18 cartridge. The recovery of compounds varied from 98.2 to 103.2%. The linearity range for the compounds was 50-1000 ng/ml. The relative standard deviations varied from 0.1 to 5.6%. The overall limits of determination ranged from 32 to 46 ng/ml of urine and from 39 to 46 ng/ml of serum, depending of the type of drugs.

High-performance liquid chromatography of deacetylmetipranolol in plasma.

A sensitive high-performance liquid chromatographic method with electro-chemical detection is developed for the determination of deacetylmetipranolol (DMP), an active metabolite of beta-sympatholytic drug metipranolol (MP). DMP is extracted from the plasma after basifying with dichloromethane. After evaporation, the residue is reconstituted in the mobile phase, injected onto the reversed-phase ODS column and chromatographed at 50 degrees C. The sensitivity of the method is 2 ng of DMP in 1 ml plasma. Pindolol, another beta-blocking agent is used as internal standard. The method is used for a pharmacokinetic investigation of MP in healthy volunteers and in the patients with liver cirrhosis.

[Pharmacokinetics of the beta-receptor blocker metipranolol in patients with liver cirrhosis (author's transl)]. / Pharmakokinetik des beta-Rezeptorenblockers Metipranolol bei Patienten mit Leberzirrhose.

The pharmacokinetics after oral administration of the beta-blocker metipranolol (Disorat) were investigated in 20 patients with liver cirrhosis, 8 of them with portocaval shunt. Twenty healthy persons were used as controls. Kinetic data in patients were not notably different from the normal group, in particular there was no significant difference in the mean serum concentration over 24 hours. In patients with advanced disease the only noteworthy difference was an increase of the linear rate of increase of serum concentrations. Maximal serum concentrations were found with a median of only 0,37 and 0,59 hours after intake, and in controls 0,76 hours after intake. It appears that metipranolol has no hepatic first-pass-effect and that its total clearance remains largely uninfluenced even in severe liver damage. A reduction of dosage in these diseases is thus not required from the pharmacological point of view.