Fast, simple and cost-effective determination of thiopental in human plasma by a new HPLC technique.

BACKGROUND: Thiopental is an anaesthetic drug that is largely used in both short-term and long-term infusion. After long-term infusion of thiopental, non-linear and inter-individual-dependent pharmacokinetics occur because of the saturation and/or induction of the metabolism. Clinical monitoring is important so that therapeutic adjustments can be made in many of the different pharmacological treatments, especially when long-term infusion is required. We describe a new, rapid HPLC method for the determination of plasma thiopental. METHODS: Sample preparation involved precipitation of plasma proteins using a mixture of methanol, zinc sulfate and ethylene glycol, and containing the internal standard 5-ethyl-5-p-tolyl-barbituric acid. After adding trichloroacetic acid, the sample was centrifuged and the supernatant was injected into a C(18) reversed-phase column. The mobile phase used was water-methanol-acetonitrile (50:40:10, v/v). The eluent was monitored at 290 nm. RESULTS: The calibration curve was linear from 0.2 to 100 microg/mL. Precision, calculated as the coefficient of variation (%), was in the range of 3.62-0.70% for the within-day assay and 5.77-1.51% for the between-day assay. The absolute recoveries obtained from supplemented samples were never less than 100%. CONCLUSIONS: This technique shows good reliability and seems to be suitable for a very fast and simple therapeutic monitoring of plasma thiopental.

Effect of hydroxymethylglutaryl-CoA reductase inhibitors on the functional properties of erythrocyte membranes.

We studied 56 patients affected by primary hypercholesterolemia treated with placebo for 1 month and with simvastatin (20 mg/day) or pravastatin (20 mg/day) for 6 months during a double-blind clinical trial. At 1-month intervals we determined the following parameters in the serum: total and HDL cholesterol, triglycerides, and apolipoprotein A-1 and B. At the same time intervals we also determined the cholesterol and phospholipid concentration, the Na+/K+ ATPase activity, and the fluidity of erythrocyte membranes. Our results demonstrated the following modifications in the erythrocyte membranes during simvastatin and pravastatin treatments: (1) an initial increase in cholesterol concentration and in cholesterol/phospholipid molar ratio, with a significant decrease only after 4 months; (2) a similar behavior of membrane fluidity, with an initial decrease and an elevation after 4 months; (3) an increase in the Na+/K+ ATPase activity only after 4 months. We hypothesize that simvastatin and pravastatin not only inhibit the hepatic synthesis of cholesterol, but also modify the cholesterol exchange between plasma and the erythrocyte membrane.