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摘要
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 x 4.6 mm i.d., 5 mu m 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.
- 出版日期2014-11
