Abstract
Exhaled nitric oxide (eNO) is a useful biomarker of various physiological conditions, including asthma and other pulmonary diseases. Herein a fast and sensitive analytical method has been developed for the quantitative detection of eNO based on extractive electrospray ionization mass spectrometry (EESI-MS). Exhaled NO molecules selectively reacted with 2-phenyl-4, 4, 5, 5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO) reagent, and eNO concentration was derived based on the EESI-MS response of 1-oxyl-2-phenyl-4, 4, 5, 5-tetramethylimidazoline (PTI) product. The method allowed quantification of eNO below ppb level (~0.02 ppbv) with a relative standard deviation (RSD) of 11.6%. In addition, eNO levels of 20 volunteers were monitored by EESI-MS over the time period of 10 hrs. Long-term eNO response to smoking a cigarette was recorded, and the observed time-dependent profile was discussed. This work extends the application of EESI-MS to small molecules (<30 Da) with low proton affinity and collision-induced dissociation efficiency, which are usually poorly visible by conventional ion trap mass spectrometers. Long-term quantitative profiling of eNO by EESI-MS opens new possibilities for the research of human metabolism and clinical diagnosis.
Highlights
Exhaled nitric oxide is a useful biomarker of various physiological conditions, including asthma and other pulmonary diseases
A fast and sensitive analytical method has been developed for the quantitative detection of Exhaled nitric oxide (eNO) based on extractive electrospray ionization mass spectrometry (EESI-MS)
An EESI-MS analytical method has been developed for the quantitative detection of eNO in humans based on the reaction between Nitric oxide (NO) and 2-phenyl-4, 4, 5, 5-tetramethylimidazoline-1-oxyl-3oxide (PTIO)
Summary
Exhaled nitric oxide (eNO) is a useful biomarker of various physiological conditions, including asthma and other pulmonary diseases. A fast and sensitive analytical method has been developed for the quantitative detection of eNO based on extractive electrospray ionization mass spectrometry (EESI-MS). EESI-MS requires no/minimal sample pretreatment and allows sensitive detection of both volatile and non-volatile compounds in exhaled breath in real time with high throughput. An EESI-MS analytical method has been developed for the quantitative detection of eNO in humans based on the reaction between NO and 2-phenyl-4, 4, 5, 5-tetramethylimidazoline-1-oxyl-3oxide (PTIO). Instead of traditional ESI, EESI, a representative ambient ionization method[29], was selected as the major detection tool because of its additional advantages of high tolerance to matrix effect and less contamination to the ion source, which helped to collect long-time reproducible and quantitative data
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