4.6 Article

Determination of Chiral Impurity of Naproxen in Different Pharmaceutical Formulations Using Polysaccharide-Based Stationary Phases in Reversed-Phased Mode

期刊

MOLECULES
卷 27, 期 9, 页码 -

出版社

MDPI
DOI: 10.3390/molecules27092986

关键词

naproxen; chiral separation; method optimization; polysaccharide stationary phase; reversed-phase HPLC; experimental design

资金

  1. Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences
  2. Semmelweis University School of PhD Studies [EFOP-3.6.3-VEKOP-16-2017-00009]
  3. Ministry for Innovation and Technology
  4. University of Medicine, Pharmacy, Science and Technology George Emil Palade of Targu Mures Research [511/3/17.01.2022, 10127/3/17.12.2020]

向作者/读者索取更多资源

A novel reversed-phase chiral HPLC method was developed for the enantiopurity control analysis of naproxen. The method utilized a polysaccharide-type chiral stationary phase and different mobile phase compositions to optimize the enantiomer separation.
A novel, validated, reversed-phase (RP), chiral high performance liquid chromatography (HPLC) method was developed for the enantiopurity control analysis of naproxen, a frequently used non-steroidal anti-inflammatory agent using polysaccharide-type chiral stationary phase (CSP). In the screening phase of method development, seven columns were tested in polar organic (PO) mode using mobile phases consisting of 0.1% acetic acid in methanol, ethanol, 2-propanol, and acetonitrile. Enantiorecognition was observed only in five cases. The best enantioseparation was observed on a Lux Amylose-1 column with 0.1% (v/v) acetic acid in ethanol with a resolution (R-s) of 1.24. The enantiomer elution order was unfavorable, as the distomer eluted after the eutomer. When the ethanolic mobile phase was supplemented with water, enantiomer elution order reversal was observed, indicating a difference in the enantiorecognition mechanism upon switching from PO to RP mode. Furthermore, by changing ethanol to methanol, not only lower backpressure, but also higher resolution was obtained. Subsequent method optimization was performed using a face-centered central composite design (FCCD) to achieve higher chiral resolution in a shorter analysis time. Optimized parameters offering baseline separation were as follows: Lux Amylose-1 stationary phase, thermostated at 40 degrees C, and a mobile phase consisting of methanol:water:acetic acid 85:15:0.1 (v/v/v), delivered with 0.65 mL/min flow rate. Using these optimized parameters, a R-s = 3.21 +/- 0.03 was achieved within seven minutes. The optimized method was validated according to the ICH guidelines and successfully applied for the analysis of different pharmaceutical preparations, such as film-coated tablets and gel, as well as fixed-dose combination tablets, containing both naproxen and esomeprazole.

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