A comparison of carbamazepine divitabs with carbamazepine normal formulation in psychiatric and oligophrenic patients. Preliminary pharmacokinetic results.

In an open, randomized, two-centre, cross-over study 20 patients formerly adjusted to a stable oral twice daily 200-600 mg carbamazepine dose, used ordinary tablets and divitabs (a new sustained-release formulation) for periods of three weeks, whereafter the serum level courses of carbamazepine and its metabolite carbamazepine-10,11-epoxide were measured. The mean peak/mean trough carbamazepine-serum concentration ratio was slightly lower after the intake of divitabs in comparison to normal formulation: 1.14 +/- 0.447 versus 1.23 +/- 0.545 (mean +/- SD). The mean trough levels of carbamazepine and its metabolite were 9% and 16% lower in the case of divitabs. In patients with peak/trough carbamazepine-serum level ratios of at least 1.30 after the intake of normal formulation, divitabs had a significant advantage.

Reliable routine method for the determination of antidepressant drugs in plasma by high-performance liquid chromatography.

We describe a rapid and reliable method using high-performance liquid chromatography for the simultaneous measurement of plasma concentrations of currently prescribed antidepressants and their main metabolites (amitriptyline, nortriptyline, trans-10-hydroxy-nortriptyline, clomipramine, desmethylclomipramine, imipramine, desipramine, zimeldine, norzimeldine, doxepin, desmethyldoxepin, trimipramine and mianserin). The method involves a single extraction of plasma at pH 10.1 with hexane-acetonitrile (98:2), solvent transfer to and evaporation in a disposable glass tube and subsequent chromatography of the residue on a CN bonded-phase column using acetonitrile-methanol-phosphate buffer (pH 7.0) as mobile phase. Protriptyline is used as the internal standard. Calibration curves remain linear up to at least 200 micrograms/l, detection limits are 5 micrograms/l, absolute recoveries are over 92%, and precision (coefficient of variation) is 6.9%. Norzimeldine and 10-hydroxynortriptyline show lower recoveries, protriptyline and 10-hydroxynortriptyline higher detection limits. Adsorption to glassware and chemical decomposition during analysis are shown to be negligible. Psychoactive and other drugs frequently prescribed in combination with anti-depressants have been tested for their chromatographic properties under the same conditions.

Computerized cyclic voltammetric detection after HPLC of the antineoplastic agents etoposide, teniposide, adriamycin and its metabolite adriamycinol in urine samples.

A computerized electrochemical detection system for application after HPLC, provided with a cyclic voltammetric oxidative and reductive module, is described for the on-line qualitative determination of electroactive antineoplastic agents and metabolites in urine samples, collected from cancer patients, following intravenous administration.The application of two cyclic voltammetric detection modes provides an insight into both oxidative and reductive electrode reactions of compounds, passing the detector and the occurrence of (it)reversible chemical and electrochemical processes at the electrode surface. In this way, redox properties of drugs and metabolites characteristic of their molecular structure, can be established, which may provide information related to their (enzymatic) bioactivation.In the cyclic voltammetric mode, the system permits automatic detection of a compound in the cell, recording, storage and plotting of voltammograms and calculation of the retention times, the half-wave potentials and the peak potentials of each scan of all individual compounds. For routine use, storage of 68 voltammograms on-line is sufficient for the analysis of biological samples in clinical-pharmacological research. Special attention has been paid to automatic, multi-reference-point component detection.Based on their concentrations in urine, the oxidative cyclic voltammetric mode, using a glassy carbon electrode, permits the determination of etoposide and teniposide, whereas the reductive cyclic voltammetric mode, with a static mercury drop electrode, permits the determination of adriamycin and its metabolite adriamycinol.

Influence of heparin on the assay of amitriptyline, clomipramine, and their metabolites.

In this study the effect of the use of lithium heparin containers on the plasma levels of amitriptyline, clomipramine, and their metabolites was investigated. Twenty-five patients (10 men and 15 women, mean age 51.8 +/- 14.9 years) taking either amitriptyline or clomipramine in a daily dosage varying from 50 to 250 mg entered the study after giving informed consent. From each patient, blood samples were taken in a sodium edetate container and in a lithium heparin container in random order. Parent compound levels are equal in sodium edetate and lithium heparin containers. Metabolite levels are 5.6% lower in lithium heparin containers. This difference is not considered clinically relevant.