Application Of Solid Phase Microextraction To The Analysis Of Volatile Metabolites Of Lung Cancer In The Exhaled Breath Vapor

Lung cancer is a leading cause of cancer death. Therefore, many efforts have been made to develop proper screening methods for an early diagnosis. Early diagnosis may help to reduce mortality in patients with lung cancer, and prolong the lifespan. The analysis of metabolites in lung cancer patients is noninvasive and fast, it will be an important assistant tool in early diagnosis of disease in the future. Due to the low amounts of metabolites and the complex matrix of biological sample, so, it is necessary to develop fast and reliable pretreatment methods to eliminate the matrix interference and enhance the sensitivity of biological analysis.The occurrence of solid-phase microextraction (SPME) makes it possible. The advantages of this method include solvent-free, high selectivity, simply set-up and rapidity. The SPME is compatible with separation systems, such as liquid chromatograph and gas chromatograph. Headspace solid-phase microextraction is an excellent extraction method for volatile compounds in gas samples. The volatile analytes can be absorbed on the fiber during the extraction. And, the extraction equilibrium can be reached quickly.In this paper, solid-phase micoextraction was combined with Gas chromatography-Mass spectrometry (GC-MS) for the analysis of volatile organic compounds in exhaled breath vapor (EBV) of lung cancer patients. A novel approach to analyze the component in breath gas of lung cancer patients was developed. The main study contents are listed as follows:1. Poly(Ethylene glycol dimethacrylate-methacrylic acid) monolith was synthetized on a polyethylene acrylic membrance as extraction medium. Based on the monolithic net, a polymer monolith solid-phase microextraction-GC-MS method was developed for the analysis of votalile organic compounds in human EBV samples. The method possesses many advantages, including high sensitivity and good selectivity. A series of experimental conditions were optimized, under the optimized conditions, the limit of detection (LOD), linearity, and reproducibility were evaluated to validate the proposed SPME-GC/MS method. The limit of detection is in range of0.8-28.7pg mL-1, the relative standard deviation (RSD) was less than13.8%and the recovery is between79%and107%. The concentration of volatile organic compound in exhaled breath of lung cancer patients was measured. In comparison with controls, the contents of cyclopentane, decane and pentanal in lung cancer patients were a little bit higher.2.With novel material graphene as absorbent, we developed a graphene fiber-based headspace solid-phase microextraction method, it was combined with gas chromatography-mass spectrometry for the analysis of votalile organic compounds in human breath samples. This method was used to determine the potential biomarkers in exhaled breath gas of lung cancer patients. This method is solvent free, rapid and easy to operate. The experimental condition has been optimized. Under the optinum conditions, the linearity, detection limits, recoveries and precision of the method were investigated. The detection limits of8compounds were in the range of0.3-3.9pg mL-1, the relative standard deviation (RSD) was less than16.5%and the satisfactory recoveries of the proposed method ranged from93%to118%. The new SPME method has been successfully applied to analysis of volatile compounds in real exhaled breath samples. In real samples analysis, we found that the concentration of heptanal and decane in lung cancer patients was higher than those of controls.