152302-45-9Relevant academic research and scientific papers
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 (2016/12/23)
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
PROCESSES FOR THE PREPARATION OF AGOMELATINE USING NOVEL INTERMEDIATES
-
, (2014/05/24)
Provided herein are novel, commercially viable and industrially advantageous processes for the preparation of Agomelatine or a salt thereof, in high yield and purity, using novel intermediates.
Substituted dimeric compounds
-
, (2008/06/13)
The invention relates to compound of formula (I): A—G1—Cy—G2—Cy′—G3—B??(I) wherein: A represents a grouping NR1C(Q)R2, C(Q)NR2R3or NR1C(Q)NR2R3, B represents a grouping NR1C(Q)R2, NR1C(Q)NR2R3, C(Q)NR2R3, C(Q)OR1, NR1C(Q)OR2or NR2R3, G1and G3represent an optionally substituted alkylene chain, Cy and Cy′, which are different, represent a ring structure or G2represents a chain and medicinal products containing the same are useful in treating or in preventing melatoninergic disorders.
Prediction of interindividual variation in drug plasma levels in vivo from individual enzyme kinetic data and physiologically based pharmacokinetic modeling
Bogaards, Jan J.P.,Hissink, Erna M.,Briggs, Mike,Weaver, Richard,Jochemsen, Roeline,Jackson, Peter,Bertrand, Marc,Van Bladeren, Peter J.
, p. 117 - 124 (2007/10/03)
A strategy is presented to predict interindividual variation in drug plasma levels in vivo by the use of physiologically based pharmacokinetic modeling and human in vitro metabolic parameters, obtained through the combined use of microsomes containing single cytochrome P450 enzymes and a human liver microsome bank. The strategy, applied to the pharmaceutical compound (N-[2-(7-methoxy-1-naphtyl)-ethyl]acetamide), consists of the following steps: (1) estimation of enzyme kinetic parameters K(m) and V(max) for the key cytochrome P450 enzymes using microsomes containing individual P450 enzymes; (2) scaling-up of the V(max) values for each individual cytochrome P450 involved using the ratio between marker substrate activities obtained from the same microsomes containing single P450 enzymes and a human liver microsome bank; (3) incorporation into a physiologically based pharmacokinetic model. For validation, predicted blood plasma levels and pharmacokinetic parameters were compared to those found in human volunteers: both the absolute plasma levels as well as the range in plasma levels were well predicted. Therefore, the presented strategy appears to be promising with respect to the integration of interindividual differences in metabolism and prediction of the possible impact on plasma and tissue concentrations of drugs in humans. Copyright (C) 2000 Elsevier Science B.V.
