Title:Identification and Synthesis of Process-Related Impurities in Lisdexamfetamine
Dimesylate
Volume: 20
Issue: 10
Author(s): Sagar Mandavkar, Pradip Gole, Rushikesh Pawar, Vishal Deshmukh, DVP Kishore, Nilesh L. Bonde*, Sandeep A. Kotharkar*Sunil V. Joshi*
Affiliation:
- Embio Research Centre, Embio Limited, Plot No. E-22/1, MIDC Industrial Estate, Mahad, Dist- Raigad Maharashtra,
402309, India. Head office: 501, Sentinel, 5th Floor, Hiranandani Gardens, Powai, Mumbai, 402076, India
- Embio Research Centre, Embio Limited, Plot No. E-22/1, MIDC Industrial Estate, Mahad, Dist- Raigad Maharashtra,
402309, India. Head office: 501, Sentinel, 5th Floor, Hiranandani Gardens, Powai, Mumbai, 402076, India
- Embio Research Centre, Embio Limited, Plot No. E-22/1, MIDC Industrial Estate, Mahad, Dist- Raigad Maharashtra,
402309, India. Head office: 501, Sentinel, 5th Floor, Hiranandani Gardens, Powai, Mumbai, 402076, India
Keywords:
Lisdexamfetamine, Process impurities, structural identification, positional isomer, synthesis, a mechanism for the formation of impurities.
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.
