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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 Oxidative-Degradation and Starting Materials-Attributed Impurities in Lisdexamfetamine Dimesylate

Author(s): Suryabhan B. Chaugule, Pradeep L. Gole, Siddhesh Haldankar, DVP Kishore, Nilesh L. Bonde* and Sandeep A. Kotharkar*

Volume 21, Issue 10, 2024

Published on: 04 March, 2024

Page: [847 - 858] Pages: 12

DOI: 10.2174/0115701786284263240219080226

Price: $65

Abstract

Impurities are an integral part of drug substances, even though they have not been studied in the pharmacological evaluation of the Benefit-Risk (BR) profiles. Hence, understanding their origin and controlling them have prime importance during drug substance development. The structures of some of the impurities in lisdexamfetamine dimesylate, a central nervous system stimulant drug, have been confirmed based on literature and analytical data. The study has been undertaken to evaluate impurities arising from oxidative degradation and impurities due to material attributes. All the listed impurities have been identified, synthesized, and characterized by spectral tools. We have, herein, reported the synthesis of two oxidative degradant impurities, 2-hydroxylisdexamfetamine dimesylate and 4-hydroxylisdexafetamine dimesylate. In addition, chiral isomeric impurities of lisdexamfetamine dimesylate as (S,R), (R,S) and (R,R)-lisdexamfetamine dimesylate have also been reported. These impurities have been identified, synthesized and a control strategy for mitigating risk in lisdexamfetamine dimesylate is provided.

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HPLC method for Impurity-C and Impurity-D: Column:Kinetex biphenyl (150x4.6), column temperature:35°C,Flow rate:1 ml/minute, detection wavelength: 210, mobile phase A:KH2PO4 buffer (650 mL):acetonitrile (100 mL): Methanol(50 mL):THF(50 mL), Mobile phase B: KH2PO4 buffer (400mL): acetonitrile (50 mL): Methanol (50 mL): THF(50 mL).

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