التفاصيل البيبلوغرافية
| العنوان: |
Identification and structural elucidation ofin vitrometabolites of atazanavir by HPLC and tandem mass spectrometry |
| المؤلفون: |
Lijun Wu, Roger D. Tung, Changfu Cheng, Scott L. Harbeson, Robert E. Zelle, Gary W. Bridson, Richard Gallegos |
| المصدر: |
Journal of Mass Spectrometry. 48:640-650 |
| بيانات النشر: |
Wiley, 2013. |
| سنة النشر: |
2013 |
| مصطلحات موضوعية: |
Protease, Chromatography, biology, Metabolite, medicine.medical_treatment, Cytochrome P450, Tandem mass spectrometry, High-performance liquid chromatography, Protease inhibitor (biology), Atazanavir, chemistry.chemical_compound, chemistry, Biochemistry, Structural isomer, medicine, biology.protein, Spectroscopy, medicine.drug |
| الوصف: |
Atazanavir (marketed as Reyataz®) is an important member of the human immunodeficiency virus protease inhibitor class. LC-UV-MSn experiments were designed to identify metabolites of atazanavir after incubations in human hepatocytes. Five major (M1–M5) and seven minor (M7–M12) metabolites were identified. The most abundant metabolite, M1, was formed by a mono-oxidation on the t-butyl group at the non-prime side. The second most abundant metabolite, M2, was also a mono-oxidation product, which has not yet been definitively identified. Metabolites, M3 and M4, were structural isomers, which were apparently formed by oxidative carbamate hydrolysis. The structure of M5 comprises the non-prime side of atazanavir which contains a pyridinyl-benzyl group. Metabolite M6a was formed by the cleavage of the pyridinyl-benzyl side chain, as evidenced by the formation of the corresponding metabolic product, the pyridinyl-benzoic acid (M6b). Mono-oxidation also occurred on the pyridinyl-benzyl group to produce the low abundance metabolite M8. Oxidation of the terminal methyl groups produced M9 and M10, respectively, which have low chemical stability. Trace-level metabolites of di-oxidations, M11 and M12, were also detected, but the complexity of the molecule precluded identification of the second oxidation site. To our knowledge, metabolites M6b and M8 have not been reported. Copyright © 2013 John Wiley & Sons, Ltd. |
| تدمد: |
1076-5174 |
| URL الوصول: |
https://explore.openaire.eu/search/publication?articleId=doi_________::663e7fe540ac0380e05d4780b0c1ab61
https://doi.org/10.1002/jms.3201 |
| حقوق: |
CLOSED |
| رقم الأكسشن: |
edsair.doi...........663e7fe540ac0380e05d4780b0c1ab61 |
| قاعدة البيانات: |
OpenAIRE |
