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An NMR Study of the Bortezomib Degradation under Clinical Use Conditions
Joint Authors
Pagliuca, Raffaella
Bolognese, Adele
Rotoli, Bruno
Catalano, Lucio
Petruzziello, Fara
Martorelli, Maria Carmen
Esposito, Anna
Scalfaro, Melania
Mazzarelli, Vittoria
Manfra, Michele
Ottiero, Maria
Source
Issue
Vol. 2009, Issue 2009 (31 Dec. 2009), pp.1-5, 5 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2009-04-14
Country of Publication
Egypt
No. of Pages
5
Main Subjects
Abstract EN
The (R)-3-methyl-1-((S)-3-phenyl-2-(pyrazine-2-carboxamido)propanamido)butyl-boronic acid, bortezomib (BTZ), which binds the 20S proteasome subunit and causes a large inhibition of its activity, is a peptidomimetic boronic drug mainly used for the treatment of multiple myeloma.
Commercial BTZ, stabilized as mannitol derivative, has been investigated under the common conditions of the clinical use because it is suspected to be easily degradable in the region of its boronic moiety.
Commercial BTZ samples, reconstituted according to the reported commercial instructions and stored at 4∘C, were analyzed by high-field nuclear magnetic resonance spectroscopy in comparison with identical samples bubbled with air and argon, respectively.
All the samples remained unchanged for a week.
After a month, the air filled samples showed the presence of two main degradation products (6% of starting material), the N-(1-(1-hydroxy-3-methylbutylamino)-1-oxo-3-phenylpropan-2-yl) pyrazine-2-carboxamide (BTZ1; 5%, determined from NMR integration) and the (S)-N-(1-(3-methylbutanamido)-1-oxo-3-phenylpropan-2-yl)pyrazine-2-carboxamide (BTZ2; 1%, determined from NMR integration), identified on the basis of their chemical and spectroscopic properties.
The BTZ1 and BTZ2 finding suggests that, under the common condition of use and at 4∘C, commercial BTZ-mannitol is stable for a week, and that, in time, it undergoes slow oxidative deboronation which partially inactivates the product.
Low temperature and scarce contact with air decrease the degradation process.
American Psychological Association (APA)
Bolognese, Adele& Esposito, Anna& Manfra, Michele& Catalano, Lucio& Petruzziello, Fara& Martorelli, Maria Carmen…[et al.]. 2009. An NMR Study of the Bortezomib Degradation under Clinical Use Conditions. Advances in Hematology،Vol. 2009, no. 2009, pp.1-5.
https://search.emarefa.net/detail/BIM-491958
Modern Language Association (MLA)
Bolognese, Adele…[et al.]. An NMR Study of the Bortezomib Degradation under Clinical Use Conditions. Advances in Hematology No. 2009 (2009), pp.1-5.
https://search.emarefa.net/detail/BIM-491958
American Medical Association (AMA)
Bolognese, Adele& Esposito, Anna& Manfra, Michele& Catalano, Lucio& Petruzziello, Fara& Martorelli, Maria Carmen…[et al.]. An NMR Study of the Bortezomib Degradation under Clinical Use Conditions. Advances in Hematology. 2009. Vol. 2009, no. 2009, pp.1-5.
https://search.emarefa.net/detail/BIM-491958
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-491958