Quantification of roxatidine in human plasma by liquid chromatography electrospray ionization tandem mass spectrometry: Application to a bioequivalence study

Ryu, Jin-Sook; Choi, Sang‐Jun; Lee, Heon-Woo; Choi, Su-Lim; Lee, Kyung‐Tae

doi:10.1016/j.jchromb.2008.10.023

Cited by 6 publications

(1 citation statement)

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“…Apart from this dominant product ion, another product ion at m/z 288 was also observed corresponding to loss of toluene. Similarly, such fragmentation reactions were also observed in the CID experiment of protonated roxatidine [9] (a histamine H 2 -receptor antagonist used for the treatment of peptic ulcer disease [10,11] ) containing an N-benzylpiperidine moiety, as well as in the protonated imatinib [12] (a drug used for the treatment of chronic myeloid leukemia and gastrointestinal stromal tumor [13] ) which contains an N-benzylpiperazine moiety. It can be inferred that these 'unusual' losses, or the transfer of a hydride ion from the neutral fragment to the cation species, are INC-mediated reactions.…”

Section: Introductionmentioning

confidence: 74%

Hydride transfer reactions via ion–neutral complex: fragmentation of protonated N‐benzylpiperidines and protonated N‐benzylpiperazines in mass spectrometry

2010

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An ion-neutral complex (INC)-mediated hydride transfer reaction was observed in the fragmentation of protonated N-benzylpiperidines and protonated N-benzylpiperazines in electrospray ionization mass spectrometry. Upon protonation at the nitrogen atom, these compounds initially dissociated to an INC consisting of [RC(6)H(4)CH(2)](+) (R = substituent) and piperidine or piperazine. Although this INC was unstable, it did exist and was supported by both experiments and density functional theory (DFT) calculations. In the subsequent fragmentation, hydride transfer from the neutral partner to the cation species competed with the direct separation. The distribution of the two corresponding product ions was found to depend on the stabilization energy of this INC, and it was also approved by the study of substituent effects. For monosubstituted N-benzylpiperidines, strong electron-donating substituents favored the formation of [RC(6)H(4)CH(2)](+), whereas strong electron-withdrawing substituents favored the competing hydride transfer reaction leading to a loss of toluene. The logarithmic values of the abundance ratios of the two ions were well correlated with the nature of the substituents, or rather, the stabilization energy of this INC.

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Section: Introductionmentioning

confidence: 74%