title: A High Resolution/Accurate Mass (HRAM) Data-Dependent MS3Neutral Loss Screening, Classification, and Relative Quantitation Methodology for Carbonyl Compounds in Saliva.
abstract: Reactive carbonyl compounds (RCCs) are ubiquitous in the environment and are generated endogenously as a result of various physiological and pathological processes. These compounds can react with biological molecules inducing deleterious processes believed to be at the basis of their toxic effects. Several of these compounds are implicated in neurotoxic processes, aging disorders, and cancer. Therefore, a method characterizing exposures to these chemicals will provide insights into how they may influence overall health and contribute to disease pathogenesis. Here, we have developed a high resolution accurate mass (HRAM) screening strategy allowing simultaneous identification and relative quantitation of DNPH-derivatized carbonyls in human biological fluids. The screening strategy involves the diagnostic neutral loss of hydroxyl radical triggering MS3fragmentation, which is only observed in positive ionization mode of DNPH-derivatized carbonyls. Unique fragmentation pathways were used to develop a classification scheme for characterizing known and unanticipated/unknown carbonyl compounds present in saliva. Furthermore, a relative quantitation strategy was implemented to assess variations in the levels of carbonyl compounds before and after exposure using deuterated d3-DNPH. This relative quantitation method was tested on human samples before and after exposure to specific amounts of alcohol. The nano-electrospray ionization (nano-ESI) in positive mode afforded excellent sensitivity with detection limits on-column in the high-attomole levels. To the best of our knowledge, this is the first report of a method using HRAM neutral loss screening of carbonyl compounds. In addition, the method allows simultaneous characterization and relative quantitation of DNPH-derivatized compounds using nano-ESI in positive mode. Graphical Abstract ᅟ.
authors: Masonic Cancer Center, University of Minnesota, 2231 6th Street SE, Minneapolis, MN, 55455, USA.
authors: Romel
authors: R
authors: Dator
authors: Masonic Cancer Center, University of Minnesota, 2231 6th Street SE, Minneapolis, MN, 55455, USA.
authors: Andrea
authors: A
authors: Carrà
authors: Masonic Cancer Center, University of Minnesota, 2231 6th Street SE, Minneapolis, MN, 55455, USA.
authors: Laura
authors: L
authors: Maertens
authors: Department of Analytical Chemistry, University of Turin, Via Pietro Giuria 5, 10125, Turin, Italy.
authors: Valeria
authors: V
authors: Guidolin
authors: Masonic Cancer Center, University of Minnesota, 2231 6th Street SE, Minneapolis, MN, 55455, USA.
authors: Peter W
authors: PW
authors: Villalta
authors: Masonic Cancer Center, University of Minnesota, 2231 6th Street SE, Minneapolis, MN, 55455, USA. balbo006@umn.edu.
authors: Silvia
authors: S
authors: Balbo
mesh_terms: D000428:Alcohol Drinking / Q000378:metabolism; D000447:Aldehydes / Q000032:analysis* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D006801:Humans; D007659:Ketones / Q000032:analysis* / Q000378:metabolism; D010659:Phenylhydrazines / Q000737:chemistry; D012463:Saliva / Q000737:chemistry* / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D000447:Aldehydes; D007659:Ketones; D010659:Phenylhydrazines; C004787:2,4-dinitrophenylhydrazine
keywords: Aldehydes/carbonyl compounds; DNPH-derivatization; Exposome; High resolution accurate mass data-dependent MS3 neutral loss screening; Relative quantitation