Fragmentation pathways and differentiation of positional isomers of sorafenib and structural analogues by ESI‐IT‐MSⁿ and ESI‐Q‐TOF‐MS/MS coupled with DFT calculations

Abstract

Sorafenib is an orally active multikinase inhibitor for the treatment of renal cell carcinoma. A series of sorafenib structural analogues were investigated in this work for their gas-phase fragmentation behaviors using electrospray ionization ion trap mass spectrometry and quadrupole time-of-flight mass spectrometry in the positive mode. The possible fragmentation pathways were proposed based on ESI-MS/MS data and theoretical calculation. Different from the typical α-cleavage of amide, consecutive reactions that involved elimination of H O and CH NC were observed for 2-pyridinecarboxamide derivatives, which were followed by the formation of a stabilized 7-membered ring carbocation by loss of CO. Two possible protonation sites occurred at carbonyl oxygen atoms for aryl-urea derivatives and the α-cleavage of urea was the main fragmentation pathways, which was followed by the formation of stable benzo [d] oxazole ring characteristic to aryl-urea derivatives. The relative abundance of characteristic fragment ions and the energy-resolved breakdown curves were used to distinguish the 4 sets of positional isomers of sorafenib and analogues. The methodology and results of the present work would contribute to the chemical structure identification of other structural analogues and the potential impurities presented in active pharmaceutical ingredients and drug formulations.

Intrinsically Fluorescent Anti-Cancer Drugs

“…A summary of selected spectroscopic properties of TKI’s is collected in Table 1 [ 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 ].…”

Components identification and isomers differentiation in pigeon pea (Cajanus cajan L.) leaves by LC‐MS

“…Moreover, Q‐TOF‐MS could supply accurate elemental compositions of precursor ions and fragment ions, which were useful for compounds structure identification. In addition, the ion trap mass spectrometry (IT‐MS n ) has the ability of generating fragment ions step by step through secondary or multilevel MS analysis [13]. The combination of Q‐TOF‐MS and IT‐MS n could greatly promote the identification of chemical constituents in natural herbs, especially low‐level components.…”

Fragmentation pathways of deprotonated amide‐sulfonamide CXCR4 inhibitors investigated by ESI‐IT‐MSn, ESI‐Q‐TOF‐MS/MS and DFT calculations

“…Therefore, it is very necessary and important to explore the unimolecular dissociation reactions and gain more insights into the mechanism information. The combined use of ESI‐IT‐MS n and ESI‐QTOF‐MS/MS could greatly facilitate the speculation of fragmentation pathways, which is helpful for chemical structure recognition of unknown compounds and distinguish the analogs …”