Fragmentation studies of sartans by electrospray ionization mass spectrometry

Peng, Ming; Li, S.; Wu, Jia; Guo, Yating; Cao, Shuting; Zhao, Yufen

doi:10.1002/jms.3965

Cited by 11 publications

(9 citation statements)

References 21 publications

(38 reference statements)

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“…Besides, the isotopic abundances and elemental compositions of fragment ions could also be obtained. The complementation of ESI‐QE‐Orbitrap‐MS/MS could greatly facilitate the speculation of fragmentation pathways, which is essential for the identification of unknown compounds . There were many studies already about fragmentation pathways of coumarin .…”

Section: Introductionmentioning

confidence: 99%

Fragmentation pathways of protonated coumarin by ESI‐QE‐Orbitrap‐MS/MS coupled with DFT calculations

et al. 2020

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Coumarin is one of the basic structures of naturally oxygen heterocyclic compound, which was investigated in this paper for its gas-phase fragmentation behaviors using electrospray quadrupole extractive orbitrap mass spectrometry in the positive mode.The possible fragmentation pathways were proposed based on electrospray ionization (ESI)-mass spectrometry (MS)/MS data and theory calculation. The elimination of two CO and CO 2 was observed for protonated coumarin, which was followed by the formation of a stabilized seven-, six-, and five-membered ring carbocation by loss of C2H2. The possible protonation sites occurred at Oxygen 11 atom of coumarin were the main fragmentation pathways. The relative abundance of characteristic fragment ions and the energy-resolved breakdown curves were used to confirm the cleavage mechanism of protonated coumarin. The methodology and results of present work would contribute to the chemical structure identification of other coumarins. K E Y W O R D S breakdown curves, fragmentation pathways, coumarin, DFT calculations MASS SPECTROMETRY 6 of 9 SUN ET AL. Journal of MASS SPECTROMETRY time, it should not emerge that ion D5 (m/z 91) transform into A (m/z 147), because two CO are respectively lost in path (b). After 55 eV, the relative abundance of product ions C (m/z 103) and D (m/z 91) may be decided by the above-mentioned cause. According to the maximal ΔG' of losing C 2 H 2 in Figure 3 (67.3 kcal/mol), which was lower than that of losing first CO (69.7 Kcal/mol) in Figure 1, the relative abundance of ion F (m/z 65) should be higher than B (m/z 119) and D (m/z 91). The results of relative abundance of ion F was lower than D before 140 eV, and higher after 140 eV in Figure 6. According to the maximal ΔG' in Figure 3, the maximal ΔG' of ion D (m/z 91) transformed into F (m/z 65) (67.3 kcal/mol, from ion D to TD 1 , black line) was higher than D (m/z 91) to D5 (m/z 91) (61.3 kcal/mol, from ion D to TD 4 , red line). So the process ion D to D5 was the favorite path and the result consistent with the curve of ions D (m/z 91) and F (m/z 65) when the NEC was lower than 140 eV. For the same reason, the red line part in Figure 3 (ion D transformed into D5) was a reversible reaction, on which the ions D (m/z 91) and D5 (m/z 91) could be transformed into each other. On the other hand, the black line part in Figure 3 would be an irreversible process, with losing of C 2 H 2 and ion F (m/z 65) turned to F1 (m/z 65), when the NEC was higher than 140 eV. Ion C (m/z 103) transformed into TC 1 (75.6 kcal/mol in Figure 4) and ion E2 into TE 3 (70.5 kcal/mol in Figure 5) with higher maximal ΔG' than process of losing CO 2 (ion A2 to TA 3 , 68.6 kcal/mol), both were endothermic reaction. The results were well consistent with the relative abundance of ion C (m/z 103), E (m/z 77)and G (m/z 51) in Figure 6. Therefore, it was further confirmed that the determining factor was the maximal ΔG' in each cleavage pathway for ESI mass.

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Section: Introductionmentioning

confidence: 99%

Fragmentation pathways of protonated coumarin by ESI‐QE‐Orbitrap‐MS/MS coupled with DFT calculations

et al. 2020

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“…Signals at 1.75 and 1.80 ppm (doublets) match the methyl groups and are coupled to downfield shifted signals at 6.38 and 6.40 ppm (quartets). 13 C chemical shifts at 84.60 and 84.69 ppm (Fig. S10) are deshielded due to the presence of heteroatoms (oxygen and chlorine).…”

Section: Resultsmentioning

confidence: 99%

Identification of new process-related impurity in the key intermediate in the synthesis of TCV-116

et al. 2018

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Development of safe and effective drugs requires complete impurity evaluation and, therefore, knowledge about the formation and elimination of impurities is necessary. During impurity profiling of a key intermediate during synthesis of candesartan cilexetil (1-(((cyclohexyloxy)carbonyl) oxy)ethyl 1-((2’-(2H-tetrazol-5-yl)-[1,1’-biphenyl]-4-yl) methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylate, TCV-116), a novel compound, which had not been reported previously, was observed. Structural elucidation of impurity was achieved by liquid chromatography hyphenated to different high resolution mass analyzers. Based on exact mass measurements and fragmentation pattern, a chloro alkyl carbonate ester analogue of the intermediate was identified. Structure of the impurity was confirmed by mass spectro-metric and NMR analyses of the target substance. Identified impurity could represent a hazard if it is transferred to the final API stage and its presence should be kept below allowed limits. Further investigation could reveal whether bis(1-chloroethyl) carbonate is a precursor to impurity formation. Therefore, synthesis should be regulated so as to minimize impurity production. Analysis of the final product indicated that the amount of impurity did not exceed 50 mg L−1, which represents the detection limit, determined according to the signal/noise ratio.

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“…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 …”

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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Amide-sulfonamides provide a potent anti-inflammatory scaffold targeting the CXCR4 receptor. A series of novel amide-sulfonamide derivatives were investigated for their gas-phase fragmentation behaviors using electrospray ionization ion trap mass spectrometry and quadrupole time-of-flight mass spectrometry in negative ion mode. Upon collision-induced dissociation (CID), deprotonated amidesulfonamides mainly underwent either an elimination of the amine to form the sulfonyl anion and amide anion or a benzoylamide derivative to provide sulfonamide anion bearing respective substituent groups. Based on the characteristic fragment ions and the deuterium-hydrogen exchange experiments, three possible fragmentation mechanisms corresponding to ion-neutral complexes including [sulfonyl anion/amine] complex (INC-1), [sulfonamide anion/benzoylamide derivative] complex (INC-2) and [amide anion/sulfonamide] complex (INC-3), respectively, wereproposed. These three ion-neutral complexes might be produced by the cleavages of S-N and C-N bond from the amide-sulfonamides, which generated the sulfonyl anion (Route 1), sulfonamide anion (Route 2) and the amide anion (Route 3). DFT calculations suggested that Route 1, which generated the sulfonyl anion (ion c) is more favorable. In addition, the elimination of SO 2 through a three-membered-ring transition state followed by the formation of C-N was observed for all the amidesulfonamides.

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Fragmentation studies of sartans by electrospray ionization mass spectrometry

Cited by 11 publications

References 21 publications

Fragmentation pathways of protonated coumarin by ESI‐QE‐Orbitrap‐MS/MS coupled with DFT calculations

Fragmentation pathways of protonated coumarin by ESI‐QE‐Orbitrap‐MS/MS coupled with DFT calculations

Identification of new process-related impurity in the key intermediate in the synthesis of TCV-116

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

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Fragmentation studies of sartans by electrospray ionization mass spectrometry

Cited by 11 publications

References 21 publications

Fragmentation pathways of protonated coumarin by ESI‐QE‐Orbitrap‐MS/MS coupled with DFT calculations

Fragmentation pathways of protonated coumarin by ESI‐QE‐Orbitrap‐MS/MS coupled with DFT calculations

Identification of new process-related impurity in the key intermediate in the synthesis of TCV-116

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

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