138113-09-4Relevant articles and documents
Evaluation of agomelatine stability under different stress conditions using an HPLC method with fluorescence detection: application to the analysis of tablets and human plasma
El-Shaheny
, p. 920 - 928 (2014)
A simple and highly sensitive stability-indicating HPLC method was developed and validated for the determination of the new antidepressant agent, agomelatine (AGM). Separation of AGM from its stress-induced degradation products was achieved on a BDS Hypersil phenyl column (250 mm × 4.6 mm i.d., 5 μm particle size) using methanol–0.05 M phosphate buffer of pH 2.5 (35: 65, v/v) as a mobile phase with fluorescence detection at 230/370 nm. Naproxen was used as an internal standard. The method satisfied all the validation requirements, as evidenced by good linearity (correlation coefficient of 0.9999, over the concentration range 0.4–40.0 ng/mL), accuracy (recovery average 99.55 ± 0.90%), precision (intra-day RSD 0.54–1.35% and inter-day RSD 0.93–1.26%), robustness and specificity. The stability of AGM was investigated under different ICH recommended stress conditions including acidic, alkaline, neutral, oxidative and photolytic. AGM was found to be labile to acidic and alkaline degradation and a kinetic study was conducted to explore its degradation behavior. First-order degradation rate constants and half-life times were calculated in each case. The proposed method was applied for the determination of AGM in tablets and spiked human plasma with mean percentage recoveries of 99.87 ± 0.31 (n = 3) and 102.09 ± 5.01 (n = 5), respectively. Hence, the proposed method was successfully applied for the determination of AGM in human volunteer plasma. The results were compared statistically with those obtained by a comparison HPLC method revealing no significant differences between the two methods regarding accuracy and precision. Copyright
Synthesis method of Agomelatine
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, (2018/04/01)
The invention relates to a preparation method of Agomelatine. The preparation method is characterized by comprising the following steps: halogenating 7-methoxy-naphthylamine, performing potassium vinyltrifluoroborate substituting and ammonifying and protecting acetyl, so as to obtain a product. The preparation method has the advantages of being easily available in raw materials, concise in processes, high in total yield, less in by-products and simple in aftertreatment, therefore, the preparation method is suitable for industrial production.
Preparation method of agomelatine
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Paragraph 0017; 0021; 0025, (2018/01/12)
The invention discloses a preparation method of agomelatine. In the method, 1-methyl-7-methoxynaphthalene is used as an initial raw material and is successively subjected to a bromination reaction with N-bromosuccinimide, a substitution reaction with nitromethane, a nitro-reduction reaction, and an acetylation reaction to produce a final product of agomelatine. The preparation method has fewer steps and employs low-cost and easy-to-obtained raw materials. During the reactions, high-risk and high-cost hydrogenation catalysts, such as palladium-carbon and Raney nickel, are not employed, so that the reactions are more reliable and require lower energy. The method can reduce transfer loss of intermediates, is simpler in operation, occupies fewer operators, is stable in product quality and high in yield and is suitable for large-scale industrial stable production.
