Photochemical Degradation of the Anticancer Drug Bortezomib by V-UV/UV (185/254 nm) Investigated by (1)H NMR Fingerprinting: A Way to Follow Aromaticity Evolution.
We have investigated the removal of bortezomib, an anticancer drug prescribed in multiple myeloma, using the photochemical advanced oxidation process of V-UV/UV (185/254 nm). We used two complementary analytical techniques to follow the removal rate of bortezomib. Nuclear magnetic resonance (NMR) is a nonselective method requiring no prior knowledge of the structures of the byproducts and permits us to provide a spectral signature (fingerprinting approach). This untargeted method provides clues to the molecular structure changes and information on the degradation of the parent drug during the irradiation process. This holistic NMR approach could provide information for monitoring aromaticity evolution. We use liquid chromatography, coupled with high-resolution mass spectrometry (LC-MS), to correlate results obtained by (1)H NMR and for accurate identification of the byproducts, in order to understand the mechanistic degradation pathways of bortezomib. The results show that primary byproducts come from photoassisted deboronation of bortezomib at 254 nm. A secondary byproduct of pyrazinecarboxamide was also identified. We obtained a reliable correlation between these two analytical techniques.
†Derichebourg Aqua, 1 rond point de Flotis, 31240 Saint Jean, France.|§Laboratoire des Interactions Moléculaires et Réactivité Chimique et Photochimique (IMRCP), UMR CNRS 5623, Université de Toulouse III (Paul Sabatier, UPS), 118, route de Narbonne, F-31062 Toulouse Cedex 9, France.
Marion
M
Martignac
‡Laboratoire de Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique (LSPCMIB), Goupe de RMN Biomédicale, UMR CNRS 5068, Université de Toulouse III (Paul Sabatier, UPS), 118, route de Narbonne, F-31062 Toulouse Cedex 9, France.
Stéphane
S
Balayssac
‡Laboratoire de Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique (LSPCMIB), Goupe de RMN Biomédicale, UMR CNRS 5068, Université de Toulouse III (Paul Sabatier, UPS), 118, route de Narbonne, F-31062 Toulouse Cedex 9, France.
Véronique
V
Gilard
§Laboratoire des Interactions Moléculaires et Réactivité Chimique et Photochimique (IMRCP), UMR CNRS 5623, Université de Toulouse III (Paul Sabatier, UPS), 118, route de Narbonne, F-31062 Toulouse Cedex 9, France.
Florence
F
Benoit-Marquié
D000970:Antineoplastic Agents / Q000737:chemistry; D000069286:Bortezomib / Q000737:chemistry* / Q000528:radiation effects; D002853:Chromatography, Liquid; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D055668:Photochemical Processes; D021241:Spectrometry, Mass, Electrospray Ionization; D014466:Ultraviolet Rays; D014874:Water Pollutants, Chemical / Q000737:chemistry
D000970:Antineoplastic Agents; D014874:Water Pollutants, Chemical; D000069286:Bortezomib