A simple, accurate and sensitive spectrophotometric method has been developed and validated for determination of antipsychotic drugs: Levetiracetam, Piracetam, Entacapon, and Carbamazepine. The method was based on the complexation of these drugs with Copper (II) as copper sulphate or chloride. Levetiracetam and Piracetam indirectly determined using Cu (II) Sulfate exchange complexation and subsequent measurement of the excess copper sulphate a colored compound at (λmax at 524 nm). The decrease in the absorption intensity (ΔA) of the colored copper sulphate, due to the presence of these two drugs (I or II) was correlated with their concentration in the sample solution. Entacapon and Carbamazepine react with copper chloride to give stable copper (II) complexes. The absorption intensity (λmax at 448 nm) was correlated with drugs concentration in a linear relationship. Different variables affecting the reaction were carefully studied and optimized. Relationships with good correlation coefficients (0.9985-0.9994) were found between ΔA or A values and the concentrations of the drugs. The method was validated, in terms of accuracy, precision and selectivity; the results were satisfactory. The proposed method was successfully applied to the analysis of the investigated drugs in their pure, spiked human plasma samples and pharmaceutical dosage forms. The Stoichiometry of complexes determined by Job’s method and the stability constants were calculated according to the Benesi–Hildebrand equation. The copper complexes with Entacapon and Carbamazepine are separated and characterized mainly by elemental analysis, magnetic moment, electron spin resonance spectroscopy (ESR) and Fourier transform IR (FT-IR).
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