9,10-Phenanthrenequinone as a mass-tagging reagent for ultra-sensitive liquid chromatography–tandem mass spectrometry assay of aliphatic aldehydes in human serum

• 9,10-Phenanthrenquinone is used as novel mass-tagging reagent for aldehydes.
• A new LC–MS/MS method was developed for analysis of aliphatic aldehydes.
• The method is selective and ultrasensitive with detection limits of 4–100 pM.
• Liquid–liquid extraction of aldehydes from serum is achieved with salting out assist.
• The level of C3-C10 aldehydes was determined in 14 healthy human serum samples.

9,10-Phenanthrenequinone (PQ) was successfully used as a new mass-tagging reagent for sensitive labeling of aliphatic aldehydes (C3-C10) prior liquid chromatography-electrospray ionization–tandem mass spectrometry (LC/ESI–MS/MS). This reagent could overcome the drawbacks of previous amine or hydrazine-based reagents, such as lower sensitivity, formation of two stereoisomeric reaction products for each single analyte, need for longer derivatization time, and poor reactivity with aliphatic aldehydes. The PQ-aldehyde derivatives exhibited intense [M+H]+ and a common product ion with ESI in the positive-ion mode. The derivatives were monitored at the transition of [M+H]+ → m/z 231.9 with detection limits from 4.0 to 100 pM (signal to noise ratio = 3). 3-Phenylpropanal was used as an internal standard (IS) and the separation of the eight aldehydes and IS was achieved in less than 10 min employing gradient elution with methanol and ammonium formate buffer (20 mM, pH 4.0). The method employed salting out liquid–liquid extraction for aliphatic aldehydes form serum for the first time with excellent recoveries (92.6–110.8%). The developed method was validated and applied for quantification of the target aldehydes in serum of healthy volunteers (n = 14).