Quantitative detection of nitric oxide in exhaled human breath by extractive electrospray ionization mass spectrometry

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.

Fractional exhaled nitric oxide-measuring devices: technology update

“…Recently, new feasible techniques to measure exhaled NO have been developed; these include a method based on extractive electrospray ionization mass spectrometry for quantitative detection of exhaled NO at ppb level. 49 FENO values are derived from the electrospray ionization mass spectrometry response of the product of selective reaction between 2-phenyl-4, 4, 5, 5-tetramethylimidazoline-1-oxyl-3-oxide reagent and NO molecules. However, the length of time required for sample collection and the usage of solvents hindered its application for online measurement.…”

Accurate quantification of creatinine in serum by coupling a measurement standard to extractive electrospray ionization mass spectrometry

“…All the experiments were performed using a Thermo Finnigan LTQ mass spectrometer (San Jose, CA, USA) equipped with a homemade EESI source, which is described elsewhere 24 25 26 27 28 29 . A schematic of EESI source is shown in Fig.…”

“…before complex raw samples are analysed. Recently introduced ambient ionization techniques, including desorption electrospray ionization (DESI) 17 18 19 , direct analysis in real time (DART) 20 , desorption atmospheric pressure chemical ionization (DAPCI) 21 , dielectric barrier discharge ionization (DBDI) 22 , low temperature plasma probe (LTP) 23 , easy ambient sonic-spray ionization (EASI) 24 , and extractive electrospray ionization (EESI) 25 26 27 28 29 30 , allow direct desorption/ionization of chemicals in raw samples under ambient conditions. Ambient MS methods require no or minimal sample preparation and tolerate chemical contamination of an ion source.…”

Quantitative mass spectrometry of unconventional human biological matrices

“…Potential biomarkers present in exhaled breath can be used for early diagnosis of diseases (especially lung-related) [87,88], and in toxicological investigations (e.g. exposure to tobacco smoke) [83].…”