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The study aimed to establish a high-performance liquid chromatography (HPLC) method for the quantitative analysis of the related substances of bedaquiline fumarate. Nuclear magnetic resonance and mass spectrometry were used for characterization and assay. A chromatographic method was used for separation. The conditions used were: gradient elution system composed of methanol 0.01mol/L KH2PO4 and 0.01 mol/L K2HPO4 (pH = 4.1) with a flow rate of 1 mL/min, at 224 nm as the detection wavelength. In this study, three degradation products of bedaquiline fumarate have been disclosed for the first time. The related impurities and degradation products of the drug were well separated. The method provided linear responses within the concentration range, which varied from 0.20 to 10.08 μg/mL with limits of detection of 0.10 μg/mL and limits of quantification of 0.20 μg/mL. The mean percent recovery varied between 91.64 and 105.89%. The method was validated for other parameters such as specificity, stability, and robustness. This method was validated and worked well for the impurity studies and quality control analysis of the laboratory-prepared samples of bedaquiline fumarate.

Herein we describe the development of a kilogram-scale preparation of a preferential dopamine D3 versus D2 receptor antagonist SIPI 6398 (1) as a new alternative treatment for schizophrenia. Modifi...

Enzalutamide was recently approved for the treatment of castration-resistant prostate cancer. In this study, the related substances in enzalutamide bulk substance were analyzed qualitatively and quantitatively. Four degradation products (Oxi, A9, P1 and P2) of enzalutamide were isolated using semi-preparative liquid chromatography and characterized using nuclear magnetic resonance and mass spectrometry. In addition, two reversed-phase liquid chromatography methods were developed for quantification of 13 potential impurities and the main constituent, respectively. These two methods were validated and applied during the impurity studies and quality control analysis of the laboratory-prepared samples of enzalutamide.

A series of novel aralkyl piperazine derivatives were synthesized, and evaluated for their serotonin reuptake inhibitory and 5-HT1A/5-HT7 receptors affinities activity. Antidepressant activities in vivo of the compounds were screened using the forced swimming test (FST) and tail suspension test (TST). The results indicated that compounds 21k (RUI, IC50 = 31 nM; 5-HT1A, 5-HT7, ki = 62, 12 nM) and 21n (RUI, IC50 = 25 nM; 5-HT1A, 5-HT7, ki = 28, 3.3 nM) exhibited high affinities for the 5-HT1A/5-HT7 receptors coupled with potent serotonin reuptake inhibition. Specifically, the most promising compound 21n possessed a good oral pharmacokinetic properties and an acceptable hERG profile, and showed potent antidepressant-like effect in the FST and TST models.

An improved and practical synthesis of enzalutamide was accomplished in five steps. Starting from 4-bromo-2-fluoro-benzonic acid, a methyl esterification, Ullmann ligation, methyl esterification, ring closing reaction and final methyl amidation provided the target in 35% total yield with 99.8% purity. Five identified impurities were also synthesized. This efficient and economical procedure avoids the use of highly toxic reagents and multiple recrystallization operations, which is suitable for further industrialization.

A series of novel aralkyl piperazine and piperidine derivatives were synthesized, and evaluated for their serotonin reuptake inhibitory and 5-HT

A series of novel aralkyl piperazine derivatives were synthesized, and evaluated for their serotonin reuptake inhibitory and 5-HT

A series of novel aralkyl piperazine and piperidine derivatives were synthesized, and evaluated for their serotonin reuptake inhibitory and 5-HT1A/5-HT7 receptors affinities activity. Antidepressant activities in vivo of the selective compound were screened using the forced swimming test (FST) and tail suspension test (TST). The results indicated that compound 19a exhibited high affinities for the 5-HT1A/5-HT7 receptors (5-HT1A, Ki = 12 nM; 5-HT7, Ki = 3.2 nM) coupled with potent serotonin reuptake inhibition (IC50 = 14 nM) and showed a marked antidepressant-like effect in the FST and TST models.