High-throughput screening and quantitation of guanidino and ureido compounds using liquid chromatography-drift tube ion mobility spectrometry-mass spectrometry.

The present work focused on the high-throughput screening and quantitation of guanidino compounds (GCs) and ureido compounds (UCs) in human thyroid tissues. The strategy employed benzylic rearrangement stable isotope labeling (BRSIL) for the sample preparation and then detection using liquid chromatography-drift tube ion mobility spectrometry-quadrupole time of flight mass spectrometry (LC-DTIMS-QTOF MS). A short reversed-phase LC realized an on-line desalting and a measurement cycle of 5.0 min. DTIMS separation enhanced the better specificity and selectivity for the benzil labeled GCs and UCs. The elevated mass resolution of QTOF MS enabled measure of the characteristic ions at accurate mass in MS and tandem MS spectra. Collision cross section (CCS) from DTIMS and accurate mass from QTOF MS were used as two qualifiers for the profiling and identification of GCs and UCs. In addition, an integral abundance arising from 3-D ion features (retention time, drift time, m/z) was applied to quantify the GCs and UCs in human thyroid tissues. The quantitative validation indicated good linearity (coefficient values ≥ 0.9981), good precision (1.0%-12.3% for intra-day and 0.9%-7.8% for inter-day) and good accuracy (91%-109%). The results demonstrated that the developed BRSIL coupled with LC-DTIMS-QTOF MS can be a powerful analysis platform to investigate GCs and UCs in human thyroid tissues.

Chromatographic peak reconstruction algorithm to improve qualitative and quantitative analysis of trace pesticide residues.

RATIONALE: In order to improve analysis of analytes in trace amounts in a complex matrix, we developed a novel post-processing method, named Chromatographic Peak Reconstruction (CPR), to process the recorded data from gas chromatography/time-of-flight mass spectrometry (GC/TOFMS). METHODS: For a trace ion, the relative deviation (δ) between the adjacent scanned mass-to-charge ratios (m/z) was found to be inversely proportional to its MS peak intensity. Based on this relationship, the thresholds of δ value within the specified intensity segments were estimated by the CPR and used to screen out the suspicious scan-points in the extracted ion chromatographic (EIC) peak. Then, the intensities of these suspicious scan-points were calibrated to reconstruct a new EIC peak. RESULTS: In the qualitative analysis of 118 pesticides, 107 out of the test pesticides can be confirmed. The corrected response ratios of the qualitative ion (q) over the quantitative ion (Q), q/Q, became closer to their references. In the quantitative analysis of 10 test pesticides at 5 ppb, the relative errors of the calculated concentrations after using the CPR were below ±1.55%, down from ±2.29% without using the CPR. CONCLUSIONS: The developed CPR showed great potential in the analysis of trace analytes in complex matrices. It was proved to be a helpful data processing method for the monitoring of trace pesticide residues. Copyright © 2016 John Wiley & Sons, Ltd.

Benzylic rearrangement stable isotope labeling for quantitation of guanidino and ureido compounds in thyroid tissues by liquid chromatography-electrospray ionization mass spectrometry.

Benzylic rearrangement stable isotope labeling (BRSIL) was explored to quantify the guanidino and ureido compounds (GCs and UCs). This method employed a common reagent, benzil, to label the guanidino and ureido groups through nucleophilic attacking then benzylic migrating. The use of BRSIL was investigated in the analysis of five GCs (creatine, l-arginine, homoarginine, 4-guanidinobutyric acid, and methylguanidine) and two UCs (urea and citrulline). The labeling was found simple and specific. The introduction of bi-phenyl group and the generation of nitrogen heterocyclic ring in the benzil-d0/d5 labeled GCs and UCs improved the retention behaviors in liquid chromatography (LC) and increased the sensitivity of electrospray ionization mass spectrometry (ESI MS) detection. The fragment ion pairs of m/z 182/187 and m/z 210/215 from the benzil-d0/d5 tags facilitated the discovery of potential GCs and UCs candidates residing in biological matrices. The use of BRSIL combined with LC-ESI MS was applied for simultaneously quantitation of GCs and UCs in thyroid tissues. It was demonstrated that nine GCs and UCs were detected, six of which were further quantified based on corresponding standards. It was concluded that five GCs and UCs (l-arginine, homoarginine, 4-guanidinobutyric acid, methylguanidine, and citrulline) were statistically significantly different (p < 0.05) between the para-carcinoma and carcinoma thyroid tissue samples.