Photodegradation of aqueous argatroban investigated by LC/MSn: Photoproducts, transformation processes and potential implications.
J Pharm Biomed Anal
; 131: 223-232, 2016 Nov 30.
Article
en En
| MEDLINE
| ID: mdl-27599353
ABSTRACT
Argatroban (ARGA), used as intravenous anticoagulant drug, has been reported to photodegrade under light exposure, requiring specific precautions at handling, storage and administration. Thus, for the first time, aqueous ARGA photodegradation under aerobic conditions has been described in terms of photoproducts, phototransformation processes and potential implications. ARGA significant photoproducts were successfully separated and characterized by gradient reversed-phase liquid chromatography coupled with high-resolution multistage mass spectrometry (LC/HR-MSn). Hitherto still not available in literature, ARGA in-depth fragmentation study was conducted so as to thoroughly sort out the main mechanisms specific to the molecule and therefore, to propose a fragmentation pattern relevant to the identification of ARGA related substances. Thereafter, in view of the structural characteristics of the photoproducts formed, ARGA photodegradation pathways could be worked out, showing that whether by direct photolysis or through photosensitization, the methyltetrahydroquinoline nitrogen and that of guanidine group would be mainly involved in photolysis initiation reactions, through one-electron oxidation along with proton loss. Desulfonation, cyclisation affording compounds of diazinane type, and/or rearrangements with transfer of the methyltetrahydroquinoline group toward the guanidine function were observed accordingly. Having a good insight into ARGA photodegradation pathways allows for consistent measures in view of mitigating or avoiding the drug decay and the related potential effects.
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1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fotólisis
/
Ácidos Pipecólicos
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
J Pharm Biomed Anal
Año:
2016
Tipo del documento:
Article