Thermal-assisted gasification injector for analyzing high-salt solution samples: a novel device developed for online coupling of liquid chromatography with direct analysis in real time mass spectrometry

Abstract

The presence of inorganic buffer salts in samples or the mobile phase of liquid chromatography has been a serious problem for mass spectrometry and liquid chromatography combined with mass spectrometry due to their less or non-volatility and ionization suppression. In order to solve this problem, in this study, a novel thermal-assisted gasification (TAG) injector was designed to apply online coupling of liquid chromatography (LC) and real time mass spectrometry (DART-MS). An analytical strategy for liquid chromatography coupled with direct analysis in real time mass spectrometry (LC-DART-MS) was developed using this TAG injector. Reserpine as the reference standard was used to investigate the characteristics of the TAG and to optimize the experimental parameters, including the heating temperature, the sheath gas pressure, the positions of the DART and TAG injector, and the DART temperature. A high signal-to-noise ratio of reserpine was obtained under the conditions of phosphate buffered saline (PBS), which contained 137 mM NaCl, 2.7 mM KCl, 10 mM Na₂HPO₄, and 2 mM KH₂PO₄. The heating temperature and sheath gas pressure of the TAG injector are the main influence factors on the signal intensity of the analyte. Six benzodiazepine samples (diazepam, chlordiazepoxide, midazolam, oxazepam, clonazepam, and nitrazepam) were separated and detected with the LC-DART-MS analytical strategy under a mobile phase of 10 mM phosphate buffer. The lowest limits of detection and quantitation in benzodiazepine analysis were about 10 ng mL⁻¹ and 20 ng mL⁻¹, respectively. The results showed that LC-DART-MS with TAG could be applied to analyze these samples from different matrices such as an inorganic salts buffer or weak polar solvent, while in these cases applying liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) couldn't perform well. Moreover, a method based on TAG-DART-MS for investigating DNA methylation degree in the whole cell has been established, and shows potential application in some bio-matrices.