The Analysis Of Aldehydes As Potential Biomarkers And Environmental Pollutants

Low-molecular-mass aldehydes(LMMAs)have significant cytotoxicity,mutagenicity and carcinogenicity,which are closely related to a variety of diseases.However,due to the strong hydrophilicity,high volatility and lack of chromophore or fluorophore of aldehydes,derivatization is generally required before analysis and detection.In this paper,we use a novel hydroxylamine reagent,4-((hydroxyamino)butyl)-7-hydroxycoumarin(HAHC),to label LMMAs to generate nitrone derivatives with good fluorescence performance and mass spectrometric response,followed by high performance liquid chromatography-fluorescence detection(HPLC-FLD)and liquid chromatography-mass spectrometry(LC-MS).The methods were validated and successfully applied to analyze human serum samples and environmental dust samples.The main content is as follows:(1)A nitrone formation derivatization method was established for the qualitative and quantitative analysis of 9 linear aliphatic aldehydes(acetaldehyde,propanal,butanal,pentanal,hexanal,heptanal,octanal,nonanal and decanal,C2-C10)using HAHC combined with HPLC-FLD.The detection limits were low(0.2-1 nmol/L),the reproducibilities were high(RSDs% 1.49-4.93%)and the accuracies were good(Recoveries% 81.96-111.55%).We used this method to analyze 120 serum samples from healthy,hypertension(HTN)and diabetes mellitus(DM)patients.The Receiver Operating Characteristic(ROC)and Partial Least Squares Discriminant Analysis(PLS-DA)results showed that heptanal(C7)can be used as a biomarker of HTN,butyral(C4)and valeraldehyde(C5)are biomarkers of DM.(2)Based on the above established nitrone formation method,the qualitative and quantitative analysis of four unsaturated aldehydes(4-hydroxy-2-hexenal,4-HNE,4-hydroxy-2-nonenal,4-HNE,trans-2-hexenal,T2 H and trans-2-nonenal,T2N)was carried out.The detection limits of this method were low(0.5-1 nmol/L),the reproducibilities were high(RSDs% 3.75-6.13%)and the accuracies were good(Recoveries% 81.18-110.36%).Using this method,we detected 4 unsaturated aldehydes in 90 human serum samples from healthy,HTN and DM patients.According to the statistical results,we found that 4-HHE and T2 H were proved to be unsaturated aldehydes biomarkers of HTN and T2 N may be a biomarker of DM.(3)Because HAHC labeling can effectively improve the mass spectrometric response of aldehydes,we thus investigated the aldehydes detection using LC-MS.19 kinds of LMMAs pollutants(methanal-decanal,4-hydroxy-2-hexenal,4-hydroxy-2-nonenal,trans-2-hexenal,trans-2-nonenal,trans,trans-2,4-heptadienal,trans,trans-2,4-decadienal,benzaldehyde,phenylacetaldehyde and phenylpropyl aldehyde)in environmental dust samples were successfully determined.The detection limit of this method was as low as 0.1 nmol/L,the reproducibilities were high(RSDs%0.63-7.78%),and the accuraies of the method were good(Recoveries%83.69-110.58%).We finally used this method to detect and analyze 84 dust samples from three stations in Wuhan subway in 4 different seasons.The results showed that14 kinds of aldehydes were found in the dust samples,and their levels differed from those of different stations.The aldehyde contents in spring and summer are mostly higher than those in autumn and winter.In the samples from 2 stations,the primary carcinogen formaldehyde was detected with concentrations exceed the formaldehyde concentration in air.