Design of experiments-assisted UPLC method for quantification of nitrosamine impurities in glimepiride and lobeglitazone sulfate: A green chemistry approach
A robust ultra-performance liquid chromatography (UPLC) method was developed and systematically optimized using a Design of Experiments (DoE) approach for the simultaneous quantification of glimepiride, lobeglitazone sulfate, nitrosamine impurity-3 (IMP-3), and impurity-1 (IMP-1) in the marketed LOB...
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Elsevier
2025-06-01
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| Series: | Journal of Pharmaceutical and Biomedical Analysis Open |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2949771X25000295 |
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| author | KiranKumar Chagarlamudi Venkata Kanaka Srivani Maddala Kumaraswamy Gandla |
| author_facet | KiranKumar Chagarlamudi Venkata Kanaka Srivani Maddala Kumaraswamy Gandla |
| author_sort | KiranKumar Chagarlamudi |
| collection | DOAJ |
| description | A robust ultra-performance liquid chromatography (UPLC) method was developed and systematically optimized using a Design of Experiments (DoE) approach for the simultaneous quantification of glimepiride, lobeglitazone sulfate, nitrosamine impurity-3 (IMP-3), and impurity-1 (IMP-1) in the marketed LOBG-G1 formulation. Critical method parameters, including organic phase composition, flow rate, and mobile phase pH, were identified through a comprehensive risk assessment and subsequently optimized using a Box-Behnken design. The final chromatographic conditions—50 % organic phase composition, a flow rate of 0.2 mL/min, and a mobile phase pH of 2.6—ensured efficient separation and quantification of all four analytes. The method was validated in accordance with ICH guidelines, demonstrating excellent linearity (r² > 0.999), high accuracy, and precision, with low relative standard deviation values. Stability studies conducted under different stress conditions revealed significant degradation of all four compounds in acidic, alkaline, and oxidative environments. Degradation products were further characterized using LC-MS/MS analysis, confirming their structural identity. In addition to its analytical performance, the method's environmental sustainability was evaluated using multiple green analytical chemistry assessment tools. The DoE-guided UPLC method offers a highly sensitive, selective, and reproducible analytical platform for the detection of nitrosamine impurities in antidiabetic drugs, providing enhanced method understanding while aligning with sustainability principles. |
| format | Article |
| id | doaj-art-37e671482d1e483ebdb60bb89cfe18dd |
| institution | OA Journals |
| issn | 2949-771X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmaceutical and Biomedical Analysis Open |
| spelling | doaj-art-37e671482d1e483ebdb60bb89cfe18dd2025-08-20T02:15:58ZengElsevierJournal of Pharmaceutical and Biomedical Analysis Open2949-771X2025-06-01510007810.1016/j.jpbao.2025.100078Design of experiments-assisted UPLC method for quantification of nitrosamine impurities in glimepiride and lobeglitazone sulfate: A green chemistry approachKiranKumar Chagarlamudi0Venkata Kanaka Srivani Maddala1Kumaraswamy Gandla2Department of Chemistry, Vignan’s Foundation for Science Technology and Research, Vadlamudi, Guntur, Andhra Pradesh 522213, IndiaDepartment of Chemistry, Vignan’s Foundation for Science Technology and Research, Vadlamudi, Guntur, Andhra Pradesh 522213, India; Corresponding authors.Department of Pharmacy, Chaitanya (Deemed to be University), Gandipet, Himayath Nagar (Vill), Hyderabad, Telangana 500075, India; Corresponding authors.A robust ultra-performance liquid chromatography (UPLC) method was developed and systematically optimized using a Design of Experiments (DoE) approach for the simultaneous quantification of glimepiride, lobeglitazone sulfate, nitrosamine impurity-3 (IMP-3), and impurity-1 (IMP-1) in the marketed LOBG-G1 formulation. Critical method parameters, including organic phase composition, flow rate, and mobile phase pH, were identified through a comprehensive risk assessment and subsequently optimized using a Box-Behnken design. The final chromatographic conditions—50 % organic phase composition, a flow rate of 0.2 mL/min, and a mobile phase pH of 2.6—ensured efficient separation and quantification of all four analytes. The method was validated in accordance with ICH guidelines, demonstrating excellent linearity (r² > 0.999), high accuracy, and precision, with low relative standard deviation values. Stability studies conducted under different stress conditions revealed significant degradation of all four compounds in acidic, alkaline, and oxidative environments. Degradation products were further characterized using LC-MS/MS analysis, confirming their structural identity. In addition to its analytical performance, the method's environmental sustainability was evaluated using multiple green analytical chemistry assessment tools. The DoE-guided UPLC method offers a highly sensitive, selective, and reproducible analytical platform for the detection of nitrosamine impurities in antidiabetic drugs, providing enhanced method understanding while aligning with sustainability principles.http://www.sciencedirect.com/science/article/pii/S2949771X25000295GlimepirideLobeglitazone sulfateNitrosamine impuritiesDesign of ExperimentGreen analytical chemistry |
| spellingShingle | KiranKumar Chagarlamudi Venkata Kanaka Srivani Maddala Kumaraswamy Gandla Design of experiments-assisted UPLC method for quantification of nitrosamine impurities in glimepiride and lobeglitazone sulfate: A green chemistry approach Journal of Pharmaceutical and Biomedical Analysis Open Glimepiride Lobeglitazone sulfate Nitrosamine impurities Design of Experiment Green analytical chemistry |
| title | Design of experiments-assisted UPLC method for quantification of nitrosamine impurities in glimepiride and lobeglitazone sulfate: A green chemistry approach |
| title_full | Design of experiments-assisted UPLC method for quantification of nitrosamine impurities in glimepiride and lobeglitazone sulfate: A green chemistry approach |
| title_fullStr | Design of experiments-assisted UPLC method for quantification of nitrosamine impurities in glimepiride and lobeglitazone sulfate: A green chemistry approach |
| title_full_unstemmed | Design of experiments-assisted UPLC method for quantification of nitrosamine impurities in glimepiride and lobeglitazone sulfate: A green chemistry approach |
| title_short | Design of experiments-assisted UPLC method for quantification of nitrosamine impurities in glimepiride and lobeglitazone sulfate: A green chemistry approach |
| title_sort | design of experiments assisted uplc method for quantification of nitrosamine impurities in glimepiride and lobeglitazone sulfate a green chemistry approach |
| topic | Glimepiride Lobeglitazone sulfate Nitrosamine impurities Design of Experiment Green analytical chemistry |
| url | http://www.sciencedirect.com/science/article/pii/S2949771X25000295 |
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