Comparison of Ambient and Atmospheric Pressure Ion Sources for Cystic Fibrosis Exhaled Breath Condensate Ion Mobility-Mass Spectrometry Metabolomics

CHRISTINA M. JONES; ARLENE A. STECENKO; JOSÉ J. PÉREZ; NAEL A. MCCARTY; XIAOLING ZANG; MARÍA EUGENIA MONGE; FACUNDO M. FERNÁNDEZ

JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY

ELSEVIER SCIENCE INC

Lugar: Amsterdam; Año: 2017 vol. 28 p. 1489 - 1496

1044-0305

Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutationsin the gene that encodes the cystic fibrosis transmembrane conductanceregulator (CFTR) protein. The vast majority of the mortality is due to progressive lung disease. Targeted and untargeted CF breath metabolomics investigations via exhaled breath condensate (EBC) analyses have the potential to expose metabolic alterations associated with CF pathology and aid in assessing the effectiveness of CF therapies. Here, transmission-mode direct analysis in real time traveling wave ion mobility spectrometry time-of-flight mass spectrometry (TM-DART-TWIMS-TOF MS) was tested as a high-throughput alternative to conventional direct infusion (DI) electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) methods, and a critical comparison of the three ionization methods was conducted. EBC was chosen as thenoninvasive surrogate for airway sampling over expectorated sputum as EBC can be collected in all CF subjects regardless of age and lung disease severity. When using pooled EBC collected from a healthy control, ESI detected the most metabolites, APCI a log order less, and TM-DART the least. TM-DART-TWIMS-TOF MS was used to profile metabolites in EBC samples from five healthy controls and four CF patients, finding that a panel of three discriminant EBC metabolites, some of which had been previously detected by other methods, differentiatedthese two classes with excellent cross-validated accuracy.