Simultaneous voltammetric determination of levodopa, carbidopa and benserazide in pharmaceuticals using multivariate calibration.

An analytical methodology based on differential pulse voltammetry (DPV) on a glassy carbon electrode and the partial least-squares (PLS-1) algorithm for the simultaneous determination of levodopa, carbidopa and benserazide in pharmaceutical formulations was developed and validated. Some sources of bi-linearity deviation for electrochemical data are discussed and analyzed. The multivariate model was developed as a ternary calibration model and it was built and validated with an independent set of drug mixtures in presence of excipients, according with manufacturer specifications. The proposed method was applied to both the assay and the uniformity content of two commercial formulations containing mixtures of levodopa-carbidopa (10:1) and levodopa-benserazide (4:1). The results were satisfactory and statistically comparable to those obtained by applying the reference Pharmacopoeia method based on high performance liquid chromatography. In conclusion, the methodology proposed based on DPV data processed with the PLS-1 algorithm was able to quantify simultaneously levodopa, carbidopa and benserazide in its pharmaceuticals formulations using a ternary calibration model for these drugs in presence of excipients. Furthermore, the model appears to be successful even in the presence of slight potential shifts in the processed data, which have been taken into account by the flexible chemometric PLS-1 approach.

A disposable electrochemical sensor for the rapid determination of levodopa.

Levodopa (L-dopa), the biological precursor of catecholamines, is the most widely prescribed drug in the treatment of Parkinson's disease. The present work presents a proposal for the application of a gold screen-printed electrode an electrochemical sensor for monitoring L-dopa in stationary solution and a flow system. Using the electrooxidation of L-dopa at +0.63 V in acetate buffer pH 3.0 on a gold screen-printed electrode it is possible to obtain a linear calibration curve from 9.9 x 10(-5) to 1.2 x 10(-3) mol L(-1) and a detection limit of 6.8 x 10(-5) mol L(-1). Under amperometric conditions (E(app) = 0.8 V; flow rate = 14.1 mL min(-1); pH 3.0), an analytical calibration graph for l-dopa was obtained from 1.0 x 10(-6) mol L(-1) 6.6 x 10(-4) mol L(-1) with a detection limit of 9.9 x 10(-7) mol L(-1). The method was successfully applied to the determination of L-dopa in commercial dosage forms without any pre-treatment.

Effects of hormone replacement therapy on mesolimbic extracellular dopamine stress: an in vivo microdialysis study

OBJECTIVE: To determine the effects of hormone replacement therapy on dopamine (DA) release in the nucleus accumbens septi (NAS) of rats following footshock stress and to correlate these effects with locomotory behaviour. DESIGN AND METHODS: Thirty-two Long Evans rats were ovariectomized and treated with oestradiol benzoate, progesterone or oil (control group). Rats were stereotaxically implanted with guide cannulae in the NAS and dialysis probes used to sample the extra-cellular fluid (ECF). Following baseline measurements, intermittent footshocks were delivered for 10 minutes, and dialysate DA levels and locomotor activity assessed over 20 minute intervals for 2 hours by high performance liquid chromatography and a photocell activity monitor, respectively. RESULTS: At baseline, hormone replacement significantly decreased DA levels in the NAS. Oestrogen treated rats had the lowest DA release at baseline (p<0.001). Following footshock, all groups exhibited significant increases in DA levels; oestrogen treated rats showed the most significant relative increase, but absolute levels remained lowest. Locomotor activity at baseline was highest in oestrogen treated rats and showed no change after footshock, remaining higher than in other groups. All other groups showed relative increase in activity after footshock (p=0.02). CONCLUSIONS: Oestrogen pre-treatment depresses baseline DA level in the NAS, but enhances relative levels after footshock, while suppressing changes in locomotor activity. There is a general reciprocal relationship between DA levels within ECF and locomotor activity in all groups. This finding may have implications for understanding of the processes regulated by NAS dopamine, e.g. addiction or associative learning.(Au)

Efectos de la clozapina sobre diferentes receptores / Clozapine effects on different receptors

Los experimentos se realizaron, con el propósito de valorar el efecto de la clozapina sobre los receptores a dopamina, norepinefrina, glutámico, GABA y acetilcolina. Se encontró, que los desplasamientos fueron principalmente y en orden de importancia, en los receptores M1/M2 de acetilcolina, y en los receptores a dopamina; los efectos encontrados en glutámico y GABA fueron principalmente en la corteza frontal y no se observo inhibición en la unión de norepinefrina por clozapina en ninguna área estudiada. Esto sugiere una participación importante de la corteza frontal, así como la presencia de estos receptores analizados, los cuales presentan una gran homología molecular, lo que habrá que estudiar desde diferentes puntos de vista