Collision‐induced dissociation studies of caffeine in positive electrospray ionisation mass spectrometry using six deuterated isotopomers and one N1‐ethylated homologue

Abstract

As basic CID reactions of caffeine have been elucidated in this work, the developed fragmentation scheme may serve as a valuable tool for the interpretation of ESI-CID fragmentation spectra of more complex xanthine derivatives and their respective metabolites.

Tandem mass spectrometric analysis of novel caffeine scaffold‐based bifunctional compounds for Parkinson's disease

“…The product ion at m/z 414.3 is associated with a neutral loss of methyl isocyanate (O=C=NCH 3 , 57 Da) which results from a reverse Diels‐Alder rearrangement in agreement with previously reported fragmentation mechanisms of caffeine; however, Bier et al suggested this species was in equilibrium with a ring‐closed analog (shown for m/z 414.3). The ring‐closed form more closely agrees with subsequent fragmentation leading, for example, to the formation of ions m/z 386.6 and 342.5.…”

“…The ion at m/z 427.3 is further dissociated to form ions at m/z 400.5 and 398.4 due to the neutral loss of hydrogen cyanide (27 Da) and methanimine (CH 3 N, 29 Da), respectively, and these product ions were confirmed through MS 3 analysis (Figure S2A, supporting information). The elimination of carbon monoxide (CO, 28 Da) from m/z 414.3 leads to the formation of m/z 386.6, as described previously . An alternative fragmentation pathway was proposed by Thevis et al in which neutral loss of CO occurred through an open‐ring form, although it is noteworthy that the monomeric analog shown in their study was unsubstituted at the N‐1 position.…”

“…The ion observed at m/z 370.5 is proposed to result from an inner ring breakage with the neutral loss of carbon dioxide (CO 2 , 44 Da) from m/z 414.3, as proposed in Figure . Further dissociation of m/z 370.5 yields three ions: ( m/z 342.5) via elimination of carbon monoxide (CO, 28 Da), ( m/z 231.4) via loss of C 6 H 7 N 3 O (139 Da) and H 2 (2 Da), and ( m/z 177.3) via loss of C 10 H 13 N 3 O (191 Da) and H 2 (2 Da). The product ion at m/z 414.3 also gives rise to additional ions (Figure B) observed at m/z 357.3 through a reverse Diels‐Alder rearrangement with the concomitant loss of methyl isocyanate (O=C=NCH 3 , 57 Da), as described above for m/z 414.3, and m/z 304.3 via a neutral loss of C 5 H 6 N 2 O (110 Da).…”

“…Further dissociation of m/z 370.5 yields three ions: ( m/z 342.5) via elimination of carbon monoxide (CO, 28 Da), ( m/z 231.4) via loss of C 6 H 7 N 3 O (139 Da) and H 2 (2 Da), and ( m/z 177.3) via loss of C 10 H 13 N 3 O (191 Da) and H 2 (2 Da). The product ion at m/z 414.3 also gives rise to additional ions (Figure B) observed at m/z 357.3 through a reverse Diels‐Alder rearrangement with the concomitant loss of methyl isocyanate (O=C=NCH 3 , 57 Da), as described above for m/z 414.3, and m/z 304.3 via a neutral loss of C 5 H 6 N 2 O (110 Da). In the case of m/z 329.4, it is proposed that dissociation occurs at the end of the linker region to eliminate acetonitrile (CH 3 CN, 41 Da) forming the ion at m/z 288.2, which subsequently fragments with the loss of acetonitrile (CH 3 CN, 41 Da) resulting in the ion m/z 247.2.…”

“…In the case of m/z 329.4, it is proposed that dissociation occurs at the end of the linker region to eliminate acetonitrile (CH 3 CN, 41 Da) forming the ion at m/z 288.2, which subsequently fragments with the loss of acetonitrile (CH 3 CN, 41 Da) resulting in the ion m/z 247.2. The formation of m/z 136 from m/z 221.3 results from the loss of CO and O=C=NCH 3 as shown in Figure B.…”