Gas‐phase fragmentation of protonated benzodiazepines

Abstract

Protonated 1,4-benzodiazepines dissociate in the gas phase by the common pathway of CO elimination and by unique pathways dictated by the substituents; the latter typically differentiate one benzodiazepine from another. Protonated 3-dihydro-5-phenyl-1,4-benzodiazepin-2-one, the base diazepam devoid of substituents, dissociates by eliminating CO, HNCO, benzene, and benzonitrile. Mechanisms of these reactions are proposed with ionic products being resonance stabilized. The abundant [MH-CO]+ ion dissociates to secondary products via elimination of benzene, benzonitrile, the NH2 radical, and ammonia, yielding again ionic products that are stabilized by resonance.

Fragmentation of toxicologically relevant drugs in positive‐ion liquid chromatography–tandem mass spectrometry

“…This may be true for diazepam, but a similar loss of 131 Da is also observed for analogues that lack the N 1 -methyl substituent, such as nordiazepam, prazepam (after the loss of the cyclopropylmethyl group from N 1 ), and 7-aminonitrazepam (loss of 149 Da, CO, and fluorobenzonitrile) (Badawi et al, 2009;Nakamura et al, 2009). Therefore, the structure proposal (ii) in Scheme 15 seems to be more likely (Risoli et al, 2007). (Smyth, McClean, & Ramachandran, 2000).…”

“…(Smyth, McClean, & Ramachandran, 2000). In a triple-quadrupole MS-MS spectrum, next to these ions, a protonated benzonitrile with m/z 104, and an ion with m/z 231, consistent with the loss of C 2 O 2 , is observed (Risoli et al, 2007).…”

“…In addition, a fragment ion with m/z 154 is observed. Structure proposals for these fragment ions are given in Scheme 15 (Risoli et al, 2007). Writing a structure proposal for the ion with m/z 154 may serve as an example of the difficulties in finding general fragmentation rules for benzodiazepines.…”

“…Fragmentation of benzodiazepines has been systematically studied using ion-trap and Q-TOF instruments (Smyth, McClean, & Ramachandran, 2000;Smyth et al, 2004), and using a quadrupole-linear-ion-trap hybrid instrument (Risoli et al, 2007). The MS-MS fragmentation of three exemplary benzodiazepines (diazepam, oxazepam, and flunitrazepam) is discussed here.…”

Determination of the psychoactive drugs carbamazepine and diazepam in hospital effluent and identification of their metabolites

“…4, the fragmentation pathway for nordiazepam is proposed through a loss of CO and the formation of the m/z 243 fragment, followed by the loss of a Cl and formation of the m/z 208 fragment. These fragmentations were confirmed by Smyth et al (2000), Smink et al (2004) and Risoli et al (2007). A second proposed fragmentation pathway concerns the loss of OH and formation of m/z 253 ion, followed by the loss of the C 2 H 5 N 2 group and formation of the m/z 199 ion.…”