Identification, Characterization and Quantification of Process-Related and Degradation Impurities in Lisdexamfetamine Dimesylate: Identifiction of Two New Compounds
| Autor: | Sheng-Hua Gao, Pengcheng Qiu, Chunjie Zhao, Tao Zhang, Lili Meng, Fuli Zhang |
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| Rok vydání: | 2018 |
| Předmět: |
Proton Magnetic Resonance Spectroscopy
HPLC validation Pharmaceutical Science forced degradation 02 engineering and technology Lisdexamfetamine Dimesylate structural elucidation lisdexamfetamine dimesylate High-performance liquid chromatography Methanesulfonic acid impurities Article Analytical Chemistry lcsh:QD241-441 chemistry.chemical_compound 020210 optoelectronics & photonics lcsh:Organic chemistry Impurity Liquid chromatography–mass spectrometry Limit of Detection Tandem Mass Spectrometry Drug Discovery 0202 electrical engineering electronic engineering information engineering Physical and Theoretical Chemistry Carbon-13 Magnetic Resonance Spectroscopy Acetonitrile Chromatography Aqueous solution Chemistry Organic Chemistry Reproducibility of Results Chemistry (miscellaneous) Forced degradation Molecular Medicine Drug Contamination |
| Zdroj: | Molecules Molecules, Vol 23, Iss 12, p 3125 (2018) Volume 23 Issue 12 |
| ISSN: | 1420-3049 |
| Popis: | 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 &mu m) 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. |
| Databáze: | OpenAIRE |
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