Identification and Synthesis of Oxidative-Degradation and Starting Materials-Attributed Impurities in Lisdexamfetamine Dimesylate

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.

Cite this article as:

Chaugule B. Suryabhan, Gole L. Pradeep, Haldankar Siddhesh, Kishore DVP, Bonde L. Nilesh*, Kotharkar A. Sandeep*, Identification and Synthesis of Oxidative-Degradation and Starting Materials-Attributed Impurities in Lisdexamfetamine Dimesylate, Letters in Organic Chemistry 2024; 21 (10) . https://dx.doi.org/10.2174/0115701786284263240219080226