Abstract

A novel HPLC method was proposed for the quantitation of vortioxetine, which is a new antidepressant drug, in tablets. Separation was performed on a Zorbax Eclipse Plus C18 (3.5 µm particles, 4.6 × 50 mm) column at 35 °C with 1.0 mL/min flow rate and chlorpromazine was selected as internal standard. Box–Behnken design, a design of experiment (DoE) method, was applied to explore the influences of mobile phase pH, acetonitrile content and buffer concentration on chromatographic separation of vortioxetine and chlorpromazine. The optimized conditions were acetate buffer (25 mM, pH:4):acetonitrile (63.5:36.5, v/v). Retention times of chlorpromazine and vortioxetine were 3.8 and 4.6 min, respectively, and a good chromatographic separation was obtained under optimal conditions. Validation studies of the developed method were conducted according to the International Conference on Harmonization (ICH) guideline. The method was linear in the concentration range of 0.5–50 µg/mL. The detection and quantitation limits were 0.080 and 0.264 μg/mL, respectively. Recovery values within 98–102% and relative standard deviation values lower than 2% indicate the precision and accuracy of the method. The method was applied to vortioxetine tablets with no interference.

Graphic abstract

中文翻译：

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使用DoE方法开发一种简单的HPLC方法定量伏洛西汀的方法

摘要

提出了一种新的HPLC方法，用于定量伏立西汀（一种新的抗抑郁药）在片剂中的含量。在Zorbax Eclipse Plus C18（3.5 µm颗粒，4.6×50 mm）色谱柱上于35°C以1.0 mL / min的流速进行分离，并选择氯丙嗪作为内标。实验设计（DoE）方法Box–Behnken设计用于探讨流动相pH，乙腈含量和缓冲液浓度对伏替西汀和氯丙嗪色谱分离的影响。最适条件为醋酸盐缓冲液（25 mM，pH：4）：乙腈（63.5：36.5，v / v）。氯丙嗪和伏替西汀的保留时间分别为3.8和4.6分钟，并且在最佳条件下获得了良好的色谱分离。根据国际协调会议（ICH）指南对开发的方法进行了验证研究。该方法在0.5–50 µg / mL的浓度范围内是线性的。检出限和定量限分别为0.080和0.264μg/ mL。回收率在98–102％之内且相对标准偏差值小于2％，表明该方法的准确性和准确性。该方法无干扰地用于伏替西汀片。

图形摘要