title: Development of a selective ESI-MS derivatization reagent: synthesis and optimization for the analysis of aldehydes in biological mixtures.
abstract: In LC-MS, derivatization is primarily used to improve ionization characteristics, especially for analytes that are not (efficiently) ionized by ESI or APCI such as aldehydes, sugars, and steroids. Derivatization strategies are then directed at the incorporation of a group with a permanent charge. A compound class that typically requires derivatization prior to LC-MS is the group of small aliphatic aldehydes that are, for instance, analyzed as the key biomarkers for lipid peroxidation in organisms. Here we report the development of a new tailor-made, highly sensitive, and selective derivatization agent 4-(2-(trimethylammonio)ethoxy)benzenaminium halide (4-APC) for the quantification of aldehydes in biological matrixes with positive ESI-MS/ MS without additional extraction procedures. 4-APC possesses an aniline moiety for a fast selective reaction with aliphatic aldehydes as well as a quaternary ammonium group for improved MS sensitivity. The derivatization reaction is a convenient one-pot reaction at a mild pH (5.7) and temperature (10 degrees C). As a result, an in-vial derivatization can be performed before analysis with an LC-MS/MS system. All aldehydes are derivatized within 30 min to a plateau, except malondialdehyde, which requires 300 min to reach a plateau. All derivatized aldehydes are stable for at least 35 h. Linearity was established between 10 and 500 nM and the limits of detection were in the 3-33 nM range for the aldehyde derivatives. Furthermore, the chosen design of these structures allows tandem MS to be used to monitor the typical losses of 59 and 87 from aldehyde derivatives, thereby enabling screening for aldehydes. Finally, of all aldehydes, pentanal and hexanal were detected at elevated levels in pooled healthy human urine samples.
authors: Leiden/Amsterdam Center for Drug Research, Faculty of Sciences, Department of Chemistry, Section of Analytical Chemistry & Applied Spectroscopy, VU University Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands.
authors: Mark
authors: M
authors: Eggink
authors: Maikel
authors: M
authors: Wijtmans
authors: Reggy
authors: R
authors: Ekkebus
authors: Henk
authors: H
authors: Lingeman
authors: Iwan J P
authors: IJ
authors: de Esch
authors: Jeroen
authors: J
authors: Kool
authors: Wilfried M A
authors: WM
authors: Niessen
authors: Hubertus
authors: H
authors: Irth
mesh_terms: D000447:Aldehydes / Q000032:analysis* / Q000737:chemistry / Q000652:urine; D006801:Humans; D006846:Hydrocarbons, Halogenated / Q000138:chemical synthesis / Q000737:chemistry; D007659:Ketones / Q000737:chemistry; D008315:Malondialdehyde / Q000737:chemistry; D000644:Quaternary Ammonium Compounds / Q000138:chemical synthesis / Q000737:chemistry; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D000447:Aldehydes; D006846:Hydrocarbons, Halogenated; D007659:Ketones; D000644:Quaternary Ammonium Compounds; D008315:Malondialdehyde