Synthesis, Isolation, Identification and Characterization of a Drug-Excipient Interaction Degradation Impurity in Pramipexole by HPLC, LC/MS and NMR

A drug-excipient interaction impurity associated with the degradation process of pramipexole was isolated. The impurity was detected during the stability study of pramipexole extended-release tablets. It was found at a relative retention time of 0.88 with respect to pramipexole, using the pramipexol...

Full description

Saved in:
Bibliographic Details
Published inSeparations Vol. 10; no. 1; p. 7
Main Authors Al-Rifai, Nafisah, Alshishani, Anas, Saad, Bahruddin, Rasras, Anas, Zahra, Jalal, Madieh, Shadi, Darras, Fouad
Format Journal Article
LanguageEnglish
Published Basel MDPI AG 01.01.2023
Subjects
Acids
characterization
Chromatography
Degradation
Diamines
Dopamine
drug
Excipients
identification
Impurities
Ions
isolation
Mass spectrometry
Methods
NMR
Nuclear magnetic resonance
Parkinson's disease
Pharmaceuticals
pramipexole
Restless legs syndrome
synthesis
United States > US
Germany
Online AccessGet full text

Cover

More Information
Summary:A drug-excipient interaction impurity associated with the degradation process of pramipexole was isolated. The impurity was detected during the stability study of pramipexole extended-release tablets. It was found at a relative retention time of 0.88 with respect to pramipexole, using the pramipexole gradient HPLC-UV detection method described in the USP. The structure of the impurity was identified and fully characterized using high resolution mass spectrometry, IR and NMR techniques, as presented herein. The degradation impurity was identified as (S)-N2-(methoxymethyl)-N6-propyl-4,5,6,7-tetrahydro-1,3-benzothiazole-2,6-diamine. The drug-excipient interaction mechanism of its formation was proposed. An efficient and straightforward synthetic approach was developed to prepare the degradation impurity to confirm its proposed degradation pathway and structure.
ISSN:2297-8739
2297-8739
DOI:10.3390/separations10010007