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Letters in Organic Chemistry

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ISSN (Print): 1570-1786
ISSN (Online): 1875-6255

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Research Article

Identification and Synthesis of Process-Related Impurities in Lisdexamfetamine Dimesylate

Author(s): Sagar Mandavkar, Pradip Gole, Rushikesh Pawar, Vishal Deshmukh, DVP Kishore, Nilesh L. Bonde*, Sandeep A. Kotharkar* and Sunil V. Joshi*

Volume 20, Issue 10, 2023

Published on: 15 June, 2023

Page: [982 - 990] Pages: 9

DOI: 10.2174/1570178620666230511120428

Price: $65

Abstract

During the process optimization of Lisdexamfetamine dimesylate, two process impurities were observed.

Methods: These impurities remained a concern for commercialization and were isolated, on characterization, were found to be H-Lys-ε-Lys-d-amphetamine and other being its regio- isomer H-Lys-α-Lysd- amphetamine. The main target of this study was to synthesize reference compounds for HPLC analysis of these impurities produced in Lisdexamfetamine.

Result: To the best of our knowledge, these impurities are not commercially available and no synthetic methods have been reported. Both of these potential impurities were synthesized, and their structures were established by various spectral techniques.

Conclusion: Furthermore, herein we also report the synthesis of two process impurities Boc- Lys(Boc)-ε-Lys(α-Boc)-O-Nitrophenol and Boc-Lys(Boc)-α-Lys(ε-Boc)-O-Nitrophenol and their fate for the formation of impurities H-Lys-ε-Lys-d-amphetamine and H-Lys-α-Lys-d-amphetamine.

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