RESUMEN
The stability of benactyzine in a multicomponent injectable antidote formulation in deuterium oxide was studied in the presence of various concentrations of trimedoxime bromide. Benactyzine was found to be more stable in the absence of trimedoxime bromide and its degradation rate accelerated linearly with increasing concentrations of trimedoxime bromide. The main reasons for the accelerated decomposition rate of benactyzine were found to be the nucleophilic effect of the bromide ion and the oxime moiety. For each trimedoxime concentration studied, t90 for benactyzine at 25 degrees C was calculated and was found to be 5.3-1.5 years within the concentrations range of 0-120 mg/ml. Rate constants and activation energies for benactyzine degradation were determined for each of the concentrations studied.
Asunto(s)
Benactizina/química , Reactivadores de la Colinesterasa/química , Antagonistas Muscarínicos/química , Trimedoxima/química , Soluciones FarmacéuticasRESUMEN
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.