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Headspace-programmed temperature vaporization-mass spectrometry for the rapid determination of possible volatile biomarkers of lung cancer in urine

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Abstract

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.

Schematic diagram of the developed methodology

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Acknowledgments

The authors wish to thank Spain’s Ministry of Economy and Competitiveness for funding Project CTQ2013-47993-P/BQU and the Junta de Castilla y León for Project SA162U14. A. Pérez Antón is also grateful to the Spanish Ministry of Education, Culture and Sports for a research fellowship.

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Authors and Affiliations

  1. Departamento de Química Analítica, Nutrición y Bromatología, Facultad de Ciencias Químicas, Universidad de Salamanca, 37008, Salamanca, Spain

    Ana Pérez Antón, Álvaro García Ramos, Miguel del Nogal Sánchez, José Luis Pérez Pavón & Bernardo Moreno Cordero

  2. Servicio de Medicina Interna, Hospital Virgen de la Vega, Complejo Asistencial Universitario de Salamanca, 37007, Salamanca, Spain

    Ángel Pedro Crisolino Pozas

Authors
  1. Ana Pérez Antón
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  2. Álvaro García Ramos
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  3. Miguel del Nogal Sánchez
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  4. José Luis Pérez Pavón
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  5. Bernardo Moreno Cordero
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  6. Ángel Pedro Crisolino Pozas
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Correspondence to Miguel del Nogal Sánchez.

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The authors declare that they have no conflict of interest.

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Informed consent was provided by all the individuals involved in the study.

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The study was authorized by the Hospital Ethics Committee.

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Pérez Antón, A., Ramos, Á.G., del Nogal Sánchez, M. et al. Headspace-programmed temperature vaporization-mass spectrometry for the rapid determination of possible volatile biomarkers of lung cancer in urine. Anal Bioanal Chem 408, 5239–5246 (2016). https://doi.org/10.1007/s00216-016-9618-5

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  • DOI: https://doi.org/10.1007/s00216-016-9618-5

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