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Open AccessArticle

Identification, Characterization and Quantification of Process-Related and Degradation Impurities in Lisdexamfetamine Dimesylate: Identifiction of Two New Compounds

1
Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, No. 285 Gebaini Road, Shanghai 201203, China
2
College of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China
*
Authors to whom correspondence should be addressed.
Academic Editor: In-Soo Yoon
Molecules 2018, 23(12), 3125; https://doi.org/10.3390/molecules23123125
Received: 4 November 2018 / Revised: 27 November 2018 / Accepted: 27 November 2018 / Published: 29 November 2018
(This article belongs to the Special Issue Method Development and Validation in Food and Pharmaceutical Analysis)
Twelve impurities (process-related and degradation) in lisdexamfetamine dimesylate (LDX), a central nervous system (CNS) stimulant drug, were first separated and quantified by high-performance liquid chromatography (HPLC) and then identified by liquid chromatography mass spectrometry (LC-MS). The structures of the twelve impurities were further confirmed and characterized by IR, HRMS and NMR analyses. Based on the characterization data, two previously unknown impurities formed during the process development and forced degradation were proposed to be (2S)-2,6-di-(lysyl)-amino-N-[(1S)-1-methyl-2-phenyl ethyl]hexanamide (Imp-H) and (2S)-2,6-diamino-N-[(1S)-1-methyl-2-(2-hydroxyphenyl)ethyl] hexanamide (Imp-M). Furthermore, these two compounds are new. Probable mechanisms for the formation of the twelve impurities were discussed based on the synthesis route of LDX. Superior separation was achieved on a YMC-Pack ODS-AQ S5 120A silica column (250 × 4.6 mm × 5 μm) using a gradient of a mixture of acetonitrile and 0.1% aqueous methanesulfonic acid solution. The HPLC method was optimized in order to separate, selectively detect, and quantify all the impurities. The full identification and characterization of these impurities should prove useful for quality control in the manufacture of lisdexamfetamine dimesylate. View Full-Text
Keywords: lisdexamfetamine dimesylate; impurities; structural elucidation; forced degradation; HPLC validation lisdexamfetamine dimesylate; impurities; structural elucidation; forced degradation; HPLC validation
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MDPI and ACS Style

Gao, S.; Meng, L.; Zhao, C.; Zhang, T.; Qiu, P.; Zhang, F. Identification, Characterization and Quantification of Process-Related and Degradation Impurities in Lisdexamfetamine Dimesylate: Identifiction of Two New Compounds. Molecules 2018, 23, 3125.

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