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Pierre, J. M.: Extrapyramidal symptoms with atypical antipsychotics: incidence, prevention and management. Drug Saf., 2005, 28 , 191–208. Pierre J. M

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A systematic review: Antipsychotic augmentation with treatment refractory obsessive-compulsive disorder Molecular Psychiatry 11 7 622 632

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Authors: Robert Skibiński, Genowefa Misztal, Łukasz Komsta and Agata Korólczyk

Chromatographic behavior in normal-phase thin-layer chromatography has been investigated for six atypical antipsychotic drugs (amisulpride, clozapine, olanzapine, quetiapine, risperidone, and ziprasidone). The drugs were separated on silica gel, alumina, NH 2 , CN, diol, and polyamide plates with mixtures of n -hexane and six polar modifiers (acetone, dioxane, diethylamine, ethanol, isopropanol, and tetrahydrofuran) as mobile phases. The linearity of relationships between R M and volume fraction of modifier, the logarithm of the volume fraction, the molar fraction, and the logarithm of the molar fraction was tested. The results usually fitted the Snyder-Soczewiński equation, with r > 0.9. The best separation was achieved on silica gel plates with ethanol- n -hexane, 1 + 1 ( v/v ), containing 1.5% aqueous ammonia, as mobile phase.

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Authors: Slavica Oljačić, Andjela Arsić, Darija Obradović, Katarina Nikolić and Danica Agbaba

The retention behavior and lipophilicity of aripiprazole and its nine impurities as well as ziprasidone and its five impurities have been examined by thin-layer chromatography using RP-18 stationary phase and different mixtures of methanol, water, and ammonia; and ethanol, water, and ammonia as the mobile phases. In both examined chromatographic systems, linear relationships were established between retention parameters and the volume fraction of the methanol and ethanol in mobile phase (r > 0.948 for methanol and r > 0.971 for ethanol). Correlation matrices obtained between experimentally obtained lipophilicity indices (R M 0, m, and C 0) and calculated log P values showed that, for the examined antipsychotics and their impurities, R M 0 and m values are more reliable lipophilicity parameters compared to C 0 values. In addition, the performed principal component analysis (PCA) has provided new information about the similarity and differences between the tested compounds as well as the experimental lipophilicity indices and calculated log P values. The experimentally obtained R M 0 values and the computed molecular parameters of the examined compounds were further used for the quantitative structure—retention relationship (QSRR) study in order to determine the most important properties governing retention. The QSRR modeling was performed by use of the partial least squares regression, and predictive performances of the developed QSRR models were tested by use of the cross-validation and external test set prediction. The obtained results revealed that, apart from lipophilicity, topological descriptors and molecular weights of the tested compounds have the strongest influence on the retention behavior of the examined antipsychotics and their impurities in reversed-phase thin-layer chromatography. The predictive performance of the developed QSRR model suggests its applicability for a reliable prediction of the retention behavior of the congeners.

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A sensitive and precise high-performance thin-layer chromatographic (HPTLC) method has been developed for the simultaneous estimation of clozapine and aripiprazole in combination. The method employed HPTLC aluminum plates pre-coated with silica gel 60 F254 as the stationary phase, while the solvent system was toluene‒methanol‒ethyl acetate‒ammonia (6.5:2.5:1:0.1, v/v). The R F values were observed to be 0.43 and 0.60 for clozapine and aripiprazole, respectively. Densitometric analysis was carried out in absorbance mode at 218 nm. The method was linear in the range of 200–1600 ng per band for clozapine and 100-800 ng per band for aripiprazole. The stress degradation study was performed, and it was found that clozapine was susceptible to acid hydrolysis, base hydrolysis, and photolytic degradation study. Aripiprazole was susceptible to oxidative stress degradation study. The method was validated and applied successfully for the estimation of both drugs in the synthetic mixture.

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: baseline results from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial and comparison with national estimates from NHANES III. Schizophr. Res., 2005, 80 , 19–32. Goff D. C

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advance of antipsychotic drug therapy. Lancet, 2009, 373 , 4–5. Kendall T. The spurious advance of antipsychotic drug therapy Lancet

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Authors: O.M. Einhorn, K. Georgiou and A. Tompa

central stores, excessive stimulation of M3 and dopamine D2 receptors, as well as inhibition of α2 adrenergic receptors [ 7 ]. For example, clozapine is an atypical antipsychotic drug, prescribed for patients with treatment-resistant schizophrenia and

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