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
New synthesis and purification method of agomelatine
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Paragraph 0083; 0089; 0094; 0095, (2017/09/01)
The invention discloses a new method for synthesizing crystal form II agomelatine. The method comprises the following steps: performing reaction on a compound (I) serving as a raw material and hydrogen in an ammonia gas/ethanol system to obtain a compound (II); and performing reaction on a compound (II) and acetic anhydride in a sodium acetate/ethanol system to obtain a compound (III) crude product, and recrystallizing an absolute ethanol/ethyl acetate system to obtain the crystal form II agomelatine. The invention discloses a method (two-step method) for synthesizing the crystal form II agomelatine. The method is simple and safe in experimental condition, energy-saving, environment-friendly and simple in aftertreatment, the product is easily available, high in yield and high in purity, and the method is simple in process cost and suitable for industrialized mass 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.