Title:Identification and Synthesis of Oxidative-Degradation and Starting
Materials-Attributed Impurities in Lisdexamfetamine Dimesylate
Volume: 21
Issue: 10
Author(s): Suryabhan B. Chaugule, Pradeep L. Gole, Siddhesh Haldankar, DVP Kishore, Nilesh L. Bonde*Sandeep A. Kotharkar*
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
Keywords:
Lisdexamfetamine, impurities, oxidative degradation, starting material, chromatographic separation, characterization.
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.