Liquid chromatographic method for the simultaneous determination of achiral and chiral impurities of dapoxetine in approved and counterfeit products
Liquid chromatographic method for the simultaneous determination of achiral and chiral impurities of dapoxetine in approved and counterfeit products
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DOI：
10.1016/j.chroma.2020.461388
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发表时间：
2020-08-30
影响因子：
4.1
通讯作者：
Szabo, Zoltan-Istvan
中科院分区：
文献类型：
--
作者：
Toth, Gergo;Fogarasi, Erzsebet;Szabo, Zoltan-Istvan
建立并验证了一种反相高效液相色谱法，用于同时测定S-达泊沙汀的有关物质，包括R-达泊沙汀、（3S）3-（二甲氨基-3-苯基-1-丙醇）、S-3-氨基-3-苯基-1-丙醇、1-萘酚、4-苯基-2H，3 H，4 H萘并[1，2-B]吡喃和1-（2 E）-肉桂氧基萘。在筛选实验期间，七种不同的多糖型手性固定相在极性有机模式下，使用由0.1%二乙胺的甲醇、乙醇，2-丙醇和乙腈，20 ° C下流速为0.5 mL min（-1）。在Lux Cellulose-3色谱柱上以乙醇为移动的流动相，得到最佳结果。为增加两种早期洗脱杂质的保留因子，向移动的相中加入水。为了平衡增加的总分析时间，应用了更高的柱温（40 ° C）和梯度洗脱，结合"流动编程“。使用优化的条件下，基线分离所有化合物在30分钟内实现。该方法根据国际协调理事会指南Q2（R1）进行了验证，并适用于分析批准的片剂制剂和在互联网上销售的含达泊昔单抗的产品。与预期一致，在药房获得的产品中，所有监测杂质均低于0.1%。然而，当分析互联网获取的样本时，得到了有趣的结果。这些片剂含有外消旋达泊沙坦和/或高浓度的R-达泊沙坦杂质。在此基础上，采用梯度洗脱和流速程序，将多糖类手性固定相成功地应用于反相模式下对非手性和手性杂质的同时测定。该研究进一步强调了不仅非手性，而且对映体质量控制的重要性，只要伪造一个单一的对映体剂被怀疑。(c)2020 Elsevier B. V.保留所有权利。
A reversed-phase high performance liquid chromatographic method was developed and validated for the simultaneous determination of the related substances of S-dapoxetine, including R-dapoxetine, (3S)3-(dimethylamino-3-phenyl-1-propanol), S-3-amino-3-phenyl-1-propanol, 1-naphtol, 4-phenyl-2H,3H,4H naphtho[1,2-b]pyran and 1-(2E)-Cinnamyloxynaphthalene. During the screening experiments seven different polysaccharide-type chiral stationary phases (amylose-based Lux-Amylose-1, Lux-i-Amylose-1 and Lux-Amylose-2, as well as cellulose-based Lux-Cellulose-1, Lux-Cellulose-2, Lux-Cellulose-3 and LuxCellulose-4) were tested in polar organic mode using a mobile phase consisting of 0.1% diethylamine in methanol, ethanol, 2-propanol and acetonitrile with 0.5 mL min(-1) flow rate at 20 degrees C. Best results were obtained on Lux Cellulose-3 column with the ethanol-based mobile phase. To increase the retention factor of two, early-eluting impurities, water was added to the mobile phase. In order to counterbalance the increased total analysis time, higher column temperature (40 degrees C) and gradient elution, combined with flowprogramming' was applied. Using the optimized conditions baseline separations were achieved for all compounds within 30 min. The method was validated according to the International Council on Harmonization guideline Q2(R1) and applied to the analysis of an approved, tablet formulation and dapoxetine containing products sold on the internet. As expected, in the case of the pharmacy-acquired product, all of the monitored impurities were below 0.1%. However, interesting results were obtained when internet acquired samples were analyzed. These tablets contained racemic dapoxetine and/or high concentration of R-dapoxetine impurity. Based on this work polysaccharide-based chiral stationary phases can be successfully applied for the simultaneous determination of achiral and chiral impurities in reversed-phase mode applying gradient elution and flow-rate programs. The study further underlines the importance of not only achiral, but also enantiomeric quality control, whenever counterfeiting of a single enantiomeric agent is suspected. (c) 2020 Elsevier B.V. All rights reserved.