Copyright (c) 2026 L Hanmanth Rao, MOGILI PADMA, ABHISHEK SHANKAR SAXENA, SRINU KARNATI
This work is licensed under a Creative Commons Attribution 4.0 International License.
Synthesis and Characterisation of Critical Impurities in Ampicillin Trihydrate: N-Formyl Ampicilloic Acid and D-Phenylglycylampicillin
Corresponding Author(s) : L. Hanmanth Rao
Asian Journal of Chemistry,
Vol. 38 No. 2 (2026): Vol 38 Issue 2, 2026
Abstract
The current research work elucidates the identification, synthesis and characterisation of two critical impurities of ampicillin trihydrate, designated as N-formyl ampicilloic acid and D-phenylglycylampicillin (European Pharmacopoeia impurity I). The formation of N-formyl ampicilloic acid results from the cross-contamination of ampicillin trihydrate with residual formic acid, whereas D-phenylglycylampicillin arises through the amidation of amino group in the side chain of ampicillin trihydrate with D-phenylglycine methylester. These impurities substantially affect the overall quality of the ampicillin trihydrate API; therefore, their identification and control are critical. This work holds significant value for the generic pharmaceutical industry, as an efficient synthetic route for these impurities has been established using readily accessible starting materials.
Keywords
Download Citation
Endnote/Zotero/Mendeley (RIS)BibTeX
- S. Zhang, X. Liao, T. Ding and J. Ahn, Antibiotics, 13, 260 (2024); https://doi.org/10.3390/antibiotics13030260
- D.Z. Wei and L. Yang, J. Chem. Technol. Biotechnol., 78, 431 (2003); https://doi.org/10.1002/jctb.749
- D. Kaushik, M. Mohan, D.M. Borade and O.C. Swami, J. Clin. Diagn. Res., 8, ME01 (2014); https://doi.org/10.7860/JCDR/2014/8777.4356
- D. Carcione, C. Siracusa, A. Sulejmani, V. Leoni and J. Intra, Antibiotics, 10, 995 (2021); https://doi.org/10.3390/antibiotics10080995
- Ampicillin Monograph, USP Convention.United States Pharmacopeial Convention, United States Pharmacopeia-National Formulary (USP-NF), Rockville, MD, USA (2024).
- Ampicillin Monograph, European Directorate for the Quality of Medi-cines & HealthCare (EDQM), European Pharmacopoeia, Strasbourg, France: Council of Europe (2023).
- C. Suresh, D.R. Devi, B. Aegurla, A.S.K. Reddy, K.V.V.P. Rao, G.A. Kumar and K. Basavaiah, Chem. Zvesti, 77, 7961 (2023); https://doi.org/10.1007/s11696-023-03064-z
- M.I. Youshko, L.M. van Langen, E. de Vroom, F. van Rantwijk, R.A. Sheldon and V.K. Svedas, Biotechnol. Bioeng., 73, 426 (2001); https://doi.org/10.1002/bit.1076
- J.K. Blum, A.L. Deaguero, C.V. Perez and A.S. Bommarius, ChemCatChem, 2, 987 (2010); https://doi.org/10.1002/cctc.201000135
- R. Dach, J.J. Song, F. Roschangar, W. Samstag and C.H. Senanayake, Org. Process Res. Dev., 16, 1697 (2012); https://doi.org/10.1021/op300144g
- A. Illanes and A. Fajardo, J. Mol. Catal. B: Enzym., 11, 587 (2001); https://doi.org/10.1016/S1381-1177(01)00048-5
- Y. Zhu, E. Roets, Z. Ni, M.L. Moreno, E. Porqueras and J. Hoogmartens, J. Pharm. Biomed. Anal., 14, 631 (1996); https://doi.org/10.1016/0731-7085(95)01661-9
References
S. Zhang, X. Liao, T. Ding and J. Ahn, Antibiotics, 13, 260 (2024); https://doi.org/10.3390/antibiotics13030260
D.Z. Wei and L. Yang, J. Chem. Technol. Biotechnol., 78, 431 (2003); https://doi.org/10.1002/jctb.749
D. Kaushik, M. Mohan, D.M. Borade and O.C. Swami, J. Clin. Diagn. Res., 8, ME01 (2014); https://doi.org/10.7860/JCDR/2014/8777.4356
D. Carcione, C. Siracusa, A. Sulejmani, V. Leoni and J. Intra, Antibiotics, 10, 995 (2021); https://doi.org/10.3390/antibiotics10080995
Ampicillin Monograph, USP Convention.United States Pharmacopeial Convention, United States Pharmacopeia-National Formulary (USP-NF), Rockville, MD, USA (2024).
Ampicillin Monograph, European Directorate for the Quality of Medi-cines & HealthCare (EDQM), European Pharmacopoeia, Strasbourg, France: Council of Europe (2023).
C. Suresh, D.R. Devi, B. Aegurla, A.S.K. Reddy, K.V.V.P. Rao, G.A. Kumar and K. Basavaiah, Chem. Zvesti, 77, 7961 (2023); https://doi.org/10.1007/s11696-023-03064-z
M.I. Youshko, L.M. van Langen, E. de Vroom, F. van Rantwijk, R.A. Sheldon and V.K. Svedas, Biotechnol. Bioeng., 73, 426 (2001); https://doi.org/10.1002/bit.1076
J.K. Blum, A.L. Deaguero, C.V. Perez and A.S. Bommarius, ChemCatChem, 2, 987 (2010); https://doi.org/10.1002/cctc.201000135
R. Dach, J.J. Song, F. Roschangar, W. Samstag and C.H. Senanayake, Org. Process Res. Dev., 16, 1697 (2012); https://doi.org/10.1021/op300144g
A. Illanes and A. Fajardo, J. Mol. Catal. B: Enzym., 11, 587 (2001); https://doi.org/10.1016/S1381-1177(01)00048-5
Y. Zhu, E. Roets, Z. Ni, M.L. Moreno, E. Porqueras and J. Hoogmartens, J. Pharm. Biomed. Anal., 14, 631 (1996); https://doi.org/10.1016/0731-7085(95)01661-9
