Determination of genotoxic impurity of suifonate ester in sildenafil citrate by LC-MS/MS

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Author: LI Cuifen ^1, ² LI Jianhua ^1, ² CHEN Xinguo ³ RUAN Pengwu ^1, ²  QIN Fei ^1, ²

Affiliation: 1. Guangzhou Baiyunshan Pharmaceutical Holdings Co., Ltd. Baiyunshan Pharmaceutical General Factory, Guangzhou 510515, China 2. Key Laboratory of key Technology Research on Chemical Raw Materials and Preparations of Guangdong Province, Guangzhou 510515, China 3. Guangzhou Guobiao Inspection and Testing Co., Ltd, Guangzhou 510535, China

Keywords: Sildenafil citrate Genotoxic impurity Suifonate ester Ethyl 4-ethoxy-3-formylbenzenesulfonate High performance liquid chromatography mass spectromete

DOI: 10.12173/j.issn.2097-4922.202405143

Reference: LI Cuifen, LI Jianhua, CHEN Xinguo, RUAN Pengwu, QIN Fei.Determination of genotoxic impurity of suifonate ester in sildenafil citrate by LC-MS/MS[J].Yaoxue QianYan Zazhi,2024, 28(4):634-638.DOI: 10.12173/j.issn.2097-4922.202405143. [Article in Chinese]  Copied

Abstract
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Abstract

Obiective To establish an liquid chromatography mass spectromete (LC-MS/MS) method for the determination of genotoxic impurity ethyl 4-ethoxy-3-formylbenzenesulfonate in sildenafil citrate.

Methods The separation was carried out on Agilent Poroshell 120 EC-C₁₈ column (150 mm×2.1 mm, 2.7 μm) at the column temperature of 25 ℃. The mobile phase was 0.1% formic acid solution-methanol with gradient elution, the flow rate was 0.3 mL/min and the injection volume was 5 μL. The mass spectrometry was operated in electrospray ionization with multiplereactions monitoring mode .The quantitative ion pairs were m/z 259.3→203.1 and m/z 259.3→187.1.

Results Ethyl 4-ethoxy-3-formylbenzenesulfonate had a good linear relationship within the concentration range of 4.92-196.99 ng/mL (r=0.999 5). Its average recovery rate was 96.5%, and the RSD was 4.2% (n=9). The detection limit was 0.098 ng/mL and the quantification limit was 0.246 ng/mL.

Conclusion The method is simple, sensitive and reliable, which can be applied to determine genotoxic impurity ethyl 4-ethoxy-3-formylbenzenesulfonate in sildenafil citrate.

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