Structurally diagnostic ion-molecule reactions and collisionally activated dissociation of 1,4-benzodiazepines in a quadrupole ion trap mass spectrometer

Article abstract of DOI:10.1021/ac00065a035

The ion-molecule reactions of various 1,4-benzodiazepines and dimethyl ether ions were studied with a quadrupole ion trap mass spectrometer. The methoxymethylene ions of dimethyl ether selectively react with 3-hydroxy-1,4-benzodiazepines (temazepam, oxazepam) to form (M + 13)⁺ adducts by methylene substitution, and they react with 1,4-benzodiazepines that do not have hydroxyl substituents (diazepam, nordiazepam, nitrazepam) to form (M + 15)⁺ adduct by a simple methyl cation transfer. These adducts are formed by elimination of methanol or formaldehyde, respectively, from (M + CH₂OCH₃)⁺ precursor ions. Ion-molecule reactions of model compounds with dimethyl ether ions suggest that the reactive site in the formation of (M + 15)⁺ adducts is the imine functional group of the 1,4-benzodiazepines, while the reactive site for formation of (M + 13)⁺ adducts involves a functional group interaction between the hydroxyl and carbonyl functional groups. Fragmentation induced by chemical ionization and collisionally activated dissociation provides further structural information for the differentiation of 1,4-benzodiazepines. Also, the gas-phase basicities of diazepam and temazepam have been estimated by bracketing techniques to be between 220.7 and 222.2 kcal/mol.