In this work, ten possible volatile biomarkers of lung cancer (acetone, 2-butanone, ethyl acetate, 2-pentanone, 4-methyl-2-pentanone, 2-hexanone, 3-heptanone, 2-heptanone, 3-octanone, and 2-nonanone) have been analyzed to evaluate their different concentration levels in urine samples from lung cancer patients (n = 12) and healthy controls (n = 12). The volatile compounds were generated with a headspace autosampler and analyzed with a gas chromatograph equipped with a programmed temperature vaporizer and mass spectrometry detector (HS-PTV-GC-MS). With the aim of evaluating the aforementioned differences, a Mann-Whitney U test and box-plots were obtained. Very good discrimination between cancer and control groups was achieved for three (ethyl acetate, 3-heptanone, and 3-octanone) of the ten analytes studied. With a view to assigning samples to the group of healthy or ill individuals, the Wilcoxon signed-rank test has been used. In spite of the small number of urine samples assayed, the results may suggest that the studied compounds could be considered useful tools in order to discern samples and they could be employed as a complementary test in a diagnosis. Graphical abstract Classification of samples (lung cancer patients and controls) with the Wilcoxon signed rank test.

We propose a new method for the rapid determination of five volatile compounds described in the literature as possible biomarkers of lung cancer in urine samples. The method is based on the coupling of a headspace sampler, a programmed temperature vaporizer in solvent-vent injection mode, and a mass spectrometer (HS-PTV-MS). This configuration is known as an electronic nose based on mass spectrometry. Once the method was developed, it was used for the analysis of urine samples from lung cancer patients and healthy individuals. Multivariate calibration models were employed to quantify the biomarker concentrations in the samples. The detection limits ranged between 0.16 and 21 μg/L. For the assignment of the samples to the patient group or the healthy individuals, the Wilcoxon signed-rank test was used, comparing the concentrations obtained with the median of a reference set of healthy individuals. To date, this is the first time that multivariate calibration and non-parametric methods have been combined to classify biological samples from profile signals obtained with an electronic nose. When significant differences in the concentration of one or more biomarkers were found with respect to the reference set, the sample is considered as a positive one and a new analysis was performed using a chromatographic method (HS-PTV-GC/MS) to confirm the result. The main advantage of the proposed HS-PTV-MS methodology is that no prior chromatographic separation and no sample manipulation are required, which allows an increase of the number of samples analyzed per hour and restricts the use of time-consuming techniques to only when necessary. Graphical abstract Schematic diagram of the developed methodology.

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With a view to improving the sensitivity of direct coupling of a headspace sampler (HS) with a mass spectrometer (MS), here we propose the use of a programmed temperature vaporizer (PTV) in solvent-vent injection mode before the sample is introduced into the MS. This preconcentration scheme has been used for some time in many methods based on gas chromatography (GC), but to the best of our knowledge it has not yet been used in an electronic nose based on MS. The increase in the S/N ratio with the proposed instrumental configuration (HS-PTV/MS) lies between 6.9- and 22-fold. The main advantage of using this injector lies in the fact that it does not involve time-consuming steps. To check the possibilities of this methodology, saliva samples from healthy volunteers and patients with different types of illnesses (including some types of cancer) were analyzed. None of the compounds studied was detected in the samples corresponding to the healthy volunteers. One or more biomarkers, at levels ranging from 13 to 500 μg/L, were found in five of the samples from the patients. Additionally, separative analysis by HS-PTV-GC/MS was performed for confirmatory purposes and both methods provided similar results. The main advantage of the proposed methodology is that no prior chromatographic separation and no sample manipulation are required.