HPLC-MS identification of acid degradation products of dolutegravir.

Autor: Krait S; Friedrich Schiller University, Department of Pharmaceutical/Medicinal Chemistry, Philosophenweg 14, D-07743 Jena, Germany., Wissenbach DK; Institute of Forensic Medicine, Jena University Hospital, 07740 Jena, Germany., Peters FT; Institute of Forensic Medicine, Jena University Hospital, 07740 Jena, Germany., Scriba GKE; Friedrich Schiller University, Department of Pharmaceutical/Medicinal Chemistry, Philosophenweg 14, D-07743 Jena, Germany. Electronic address: gerhard.scriba@uni-jena.de.
Jazyk: angličtina
Zdroj: Journal of pharmaceutical and biomedical analysis [J Pharm Biomed Anal] 2021 Apr 15; Vol. 197, pp. 113954. Date of Electronic Publication: 2021 Feb 06.
DOI: 10.1016/j.jpba.2021.113954
Abstrakt: Dolutegravir is an integrase strand transfer inhibitor used for the treatment of human immuno-deficiency virus infections. The present study was conducted in order to identify degradation products formed in acidic solution upon heating. The structures were assigned based on low resolution collision-induced dissociation tandem mass spectra as well as high resolution higher-energy collisional dissociation tandem mass spectra. The major degradation products resulted from hydrolytic opening of the oxepine ring leading to bis-hydroxy diastereomers (DP2 and DP3) as well as a mono-hydroxy derivative (DP1) as the result of dehydration of the diastereomers. Furthermore, two carboxylic acid derivatives (DP4 and DP5) could be identified, which can be explained as the result of the hydrolysis of the exocyclic amide bond of dolutegravir and DP1, respectively. During the fragmentation process of dolutegravir and its degradation products DP1 to DP3 a formal addition of oxygen resulting in the respective carboxylic acid fragments was detected. This could be evidenced based on high resolution masses of the fragments as well as the comparison of the MS/MS spectra of the fragments with the spectra of the carboxylic acids DP4 and DP5.
Competing Interests: Declaration of Competing Interest The authors have declared no conflict of interest.
(Copyright © 2021 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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