In situ identification and quantification of genotoxic sulfonyl chloride impurity in topiramate (Topamax tablets) via LC-MS/MS
This study reports a sensitive and selective method developed and validated for the detection of process-related genotoxic impurity (PGI) formed in situ during the synthesis of topiramate API. The method utilizes benzyl amine as a derivatizing agent to enhance sensitivity. of impurity. Chromatograph...
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Elsevier
2025-12-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2215016125002870 |
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| author | Hitesh Thumbar Jayesh Dhalani Hetal Patel Bhavin Dhaduk |
| author_facet | Hitesh Thumbar Jayesh Dhalani Hetal Patel Bhavin Dhaduk |
| author_sort | Hitesh Thumbar |
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| description | This study reports a sensitive and selective method developed and validated for the detection of process-related genotoxic impurity (PGI) formed in situ during the synthesis of topiramate API. The method utilizes benzyl amine as a derivatizing agent to enhance sensitivity. of impurity. Chromatographic separation was performed on a Kromasil-C8 column (150 mm × 4.6 mm, 5 µm) with mobile phase A as 10 mM ammonium acetate containing 0.1 % formic acid in water and mobile phase B as acetonitrile (40:60 v/v). The flow rate was set at 1.2 mL/min and detection was carried out using an RI detector. Quantification was achieved using TQMS detection with electron spray ionization in MRM mode. The method exhibited excellent linearity in the range of 0.14–2.88 µg/mL with recovery between 96.82 % and 104.42 %. The method showed a detection limit of 0.0719 µg/mL and quantitation limit of 0.1438 µg/mL, making it suitable for trace-level analysis (< 1 ppm) of sulfonyl chloride in topiramate drug substance. • Derivatization with benzyl amine enhanced PGI detection sensitivity. • Separation using Kromasil-C8 column with acetonitrile/water buffer (40:60). • Detection via RI and quantification using TQMS in MRM mode. |
| format | Article |
| id | doaj-art-154eabee7f0244419b41f58b31ff9086 |
| institution | Kabale University |
| issn | 2215-0161 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Elsevier |
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| series | MethodsX |
| spelling | doaj-art-154eabee7f0244419b41f58b31ff90862025-08-20T03:27:02ZengElsevierMethodsX2215-01612025-12-011510344110.1016/j.mex.2025.103441In situ identification and quantification of genotoxic sulfonyl chloride impurity in topiramate (Topamax tablets) via LC-MS/MSHitesh Thumbar0Jayesh Dhalani1Hetal Patel2Bhavin Dhaduk3Department of Chemistry, School of Science, RK University, Rajkot, IndiaDepartment of Chemistry, School of Science, RK University, Rajkot, IndiaAnalytical Development Laboratory, Zydus Life Science Ltd, Baroda, IndiaDepartment of Chemistry, School of Science, RK University, Rajkot, India; Department of Chemical Sciences, Faculty of Science, Atmiya University, Rajkot, India; Correspoonding author.This study reports a sensitive and selective method developed and validated for the detection of process-related genotoxic impurity (PGI) formed in situ during the synthesis of topiramate API. The method utilizes benzyl amine as a derivatizing agent to enhance sensitivity. of impurity. Chromatographic separation was performed on a Kromasil-C8 column (150 mm × 4.6 mm, 5 µm) with mobile phase A as 10 mM ammonium acetate containing 0.1 % formic acid in water and mobile phase B as acetonitrile (40:60 v/v). The flow rate was set at 1.2 mL/min and detection was carried out using an RI detector. Quantification was achieved using TQMS detection with electron spray ionization in MRM mode. The method exhibited excellent linearity in the range of 0.14–2.88 µg/mL with recovery between 96.82 % and 104.42 %. The method showed a detection limit of 0.0719 µg/mL and quantitation limit of 0.1438 µg/mL, making it suitable for trace-level analysis (< 1 ppm) of sulfonyl chloride in topiramate drug substance. • Derivatization with benzyl amine enhanced PGI detection sensitivity. • Separation using Kromasil-C8 column with acetonitrile/water buffer (40:60). • Detection via RI and quantification using TQMS in MRM mode.http://www.sciencedirect.com/science/article/pii/S2215016125002870In situ identification and quantification of genotoxic sulfonyl chloride impurity in topiramate drug substance |
| spellingShingle | Hitesh Thumbar Jayesh Dhalani Hetal Patel Bhavin Dhaduk In situ identification and quantification of genotoxic sulfonyl chloride impurity in topiramate (Topamax tablets) via LC-MS/MS MethodsX In situ identification and quantification of genotoxic sulfonyl chloride impurity in topiramate drug substance |
| title | In situ identification and quantification of genotoxic sulfonyl chloride impurity in topiramate (Topamax tablets) via LC-MS/MS |
| title_full | In situ identification and quantification of genotoxic sulfonyl chloride impurity in topiramate (Topamax tablets) via LC-MS/MS |
| title_fullStr | In situ identification and quantification of genotoxic sulfonyl chloride impurity in topiramate (Topamax tablets) via LC-MS/MS |
| title_full_unstemmed | In situ identification and quantification of genotoxic sulfonyl chloride impurity in topiramate (Topamax tablets) via LC-MS/MS |
| title_short | In situ identification and quantification of genotoxic sulfonyl chloride impurity in topiramate (Topamax tablets) via LC-MS/MS |
| title_sort | in situ identification and quantification of genotoxic sulfonyl chloride impurity in topiramate topamax tablets via lc ms ms |
| topic | In situ identification and quantification of genotoxic sulfonyl chloride impurity in topiramate drug substance |
| url | http://www.sciencedirect.com/science/article/pii/S2215016125002870 |
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