Determination of drugs used as anti-Parkinson's disease drugs in urine and serum by capillary electrophoresis.

A new capillary electrophoresis method to determine simultaneously eight of the most important anti-Parkinson's disease compounds has been developed. The generic names of the drugs studied are benactyzine (BA), trihexyphenidyl (TP), fenpiverin (FP), diphemin (DF), scopolamine (BL), adiphenine (TS), diethylaminoethylester 1-phenylcyclopentane-1-carboxylate (EKK), and diethylaminoethylester tetramethoxydiphenylacetate (EKO). An untreated fused-silica capillary tube (75 microns i.d., 57 cm total length, 49.5 cm length to the detector) was used with detection at 190 nm. The optimal separation conditions were 50 mM phosphate buffer (pH 2.7) with 7 mM-beta-cyclodextrin, electrokinetic injection for 15 sec at 5 kV, temperature 25 degrees C, and 15-20 kV separation voltage. Complete separation of all compounds was achieved in less than 16 min. The procedure was applied for the determination in urine and serum. The limits of detection (LOD, S/N = 3) for serum were 209 (FP), 234 (EKO), 168 (DF), 182 (BA), 168 (TP), 220 (BL), 174 (TS), and 163 (EKK) ppb. The method can be used for the therapeutic drug monitoring of these central active cholinolytics in clinical laboratories.

Adiphenine plasma levels and blood-brain barrier crossing in the rat.

Adiphenine was administered in 3H-labelled form in doses of 15 mumole/kg intravenously to male Wistar rats. Plasma and brain levels of the unchanged drug were measured. The elimination of the 3H-labelled compound from the plasma was monophasic with a half-life of 13 minutes. The unchanged drug was detectable in the plasma for 30 minutes after the injection. The time course of brain levels of unchanged drug paralleled that found in the plasma with a half-life of 9 to 12 minutes. In all experiments, brain and plasma levels of unchanged adiphenine correlate highly.

[Interactions of some parasympatholytics and structurally similar drugs with bovine serum albumin]. / Wechselwirkungen einiger Parasympatholytika und strukturell ähnlicher Arzneimittel mit Rinderserumalbumin

The interactions of the parasympatholytic drugs adiphenin, adiphenin H and propanthelin and the structurally related compounds, diphenhydramine, D-propoxyphene and methadone with bovine serum albumin (BSA) are studied by equilibrium dialysis and ultracentrifugation. The results show that BSA has a few binding sites (n less than 10) for the mentioned drugs. The association between the compounds under study and BSA are relatively weak. The binding constants are in the range of 10(3) l/Mol.