title: Tandem mass spectrometry of nitric oxide and hydrogen sulfide releasing aspirins: a hint into activity behavior.
abstract: Aspirin (acetylsalicylic acid, ASA) is the most popular non-steroidal anti-inflammatory drug. However, due to its action on cyclooxygenase and its acid nature, aspirin is associated with adverse gastrointestinal effects. In an effort to minimize these side effects, NO-donor and H2S-donor ASA co-drugs have been designed and tested. Their mass spectrometric behavior is now analyzed and reported. Positive ions were obtained by electrospray ionization involving protonation or alkali metal attachment. Their dissociation processes have been studied by collision induced dissociation in a triple quadrupole instrument. High mass accuracy measurements have been recorded on a Fourier transform ion cyclotron resonance mass spectrometer. The protonated molecules dissociate by an exclusive or largely prevailing path leading to acetyloxy-substituted benzoyl cation, namely an ASA unit. The process is reminiscent of the enzymatic hydrolysis, releasing intact ASA to a large extent. Only at higher collision energy does the formal ketene loss disrupt the ASA moiety. The gas phase chemistry of protonated ASA-releasing drugs develops along elementary dissociation steps analogous to the reactive processes in complex biological environments. This notion may provide a tool for preliminary testing of new compounds.
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, Università degli Studi di Roma "La Sapienza"
authors.forename: Maria Elisa
authors.initials: ME
authors.lastname: Crestoni
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, Università degli Studi di Roma "La Sapienza"
authors.forename: Barbara
authors.initials: B
authors.lastname: Chiavarino
authors.affiliation: Dipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi di Torino.
authors.forename: Stefano
authors.initials: S
authors.lastname: Guglielmo
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, Università degli Studi di Roma "La Sapienza"
authors.forename: Valentina
authors.initials: V
authors.lastname: Lilla
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, Università degli Studi di Roma "La Sapienza"
authors.forename: Simonetta
authors.initials: S
authors.lastname: Fornarini
keywords: FT-ICR mass spectrometry; acetylsalicylic acid derivatives; electrospray ionization mass spectrometry; non-steroidal anti-inflammatory drugs