Biogenic aldehyde determination by reactive paper spray ionization mass spectrometry

Ionization of aliphatic and aromatic aldehydes is improved by performing simultaneous chemical derivatization using 4-aminophenol to produce charged iminium ions during paper spray ionization. Accelerated reactions occur in the microdroplets generated during the paper spray ionization event for the tested aldehydes (formaldehyde, n-pentanaldehyde, n-nonanaldehyde, n-decanaldehyde, n-dodecanaldehyde, benzaldehyde, m-anisaldehyde, and p-hydroxybenzaldehyde). Tandem mass spectrometric analysis of the iminium ions using collision-induced dissociation demonstrated that straight chain aldehydes give a characteristic fragment at m/. z 122 (shown to correspond to protonated 4-(methyleneamino)phenol), while the aromatic aldehyde iminium ions fragment to give a characteristic product ion at m/. z 120. These features allow straightforward identification of linear and aromatic aldehydes. Quantitative analysis of n-nonaldehyde using a benchtop mass spectrometer demonstrated a linear response over 3 orders of magnitude from 2.5. ng to 5. μg of aldehyde loaded on the filter paper emitter. The limit of detection was determined to be 2.2. ng for this aldehyde. The method had a precision of 22%, relative standard deviation. The experiment was also implemented using a portable ion trap mass spectrometer

Analysis of supramolecular complexes of 3-methylxanthine with field asymmetric waveform ion mobility spectrometry combined with mass spectrometry

Miniaturised field asymmetric waveform ion mobility spectrometry (FAIMS), combined with mass spectrometry (MS), has been applied to the study of self-assembling, non-covalent supramolecular complexes of 3-methylxanthine (3-MX) in the gas phase. 3-MX forms stable tetrameric complexes around an alkali metal (Na+, K+) or ammonium cation, to generate a diverse array of complexes with single and multiple charge states. Complexes of (3-MX)n observed include: singly charged complexes where n = 1-8 and 12 and doubly charged complexes where n = 12-24. The most intense ions are those associated with multiples of tetrameric units, where n = 4, 8, 12, 16, 20, 24. The effect of dispersion field on the ion intensities of the self-assembled complexes indicates some fragmentation of higher order complexes within the FAIMS electrodes (in-FAIMS dissociation), as well as in-source collision induced dissociation within the mass spectrometer. FAIMS-MS enables charge state separation of supramolecular complexes of 3-MX and is shown to be capable of separating species with overlapping mass-to-charge ratios. FAIMS selected transmission also results in an improvement in signal-to-noise ratio for low intensity complexes and enables the visualisation of species undetectable without FAIMS

Increasing peak capacity in nontargeted omics applications by combining full scan field asymmetric waveform ion mobility spectrometry with liquid chromatography–mass spectrometry

Full scan field asymmetric waveform ion mobility spectrometry (FAIMS) combined with liquid chromatography and mass spectrometry (LC-FAIMS-MS) is shown to enhance peak capacity for omics applications. A miniaturized FAIMS device capable of rapid compensation field scanning has been incorporated into an ultrahigh performance liquid chromatography (UHPLC) and time-of-flight mass spectrometry analysis, allowing the acquisition of full scan FAIMS and MS nested data sets within the time scale of a UHPLC peak. Proof of principle for the potential of scanning LC-FAIMS-MS in omics applications is demonstrated for the nontargeted profiling of human urine using a HILIC column. The high level of orthogonality between FAIMS and MS provides additional unique compound identifiers with detection of features based on retention time, FAIMS dispersion field and compensation field (DF and CF), and mass-to-charge (m/z). Extracted FAIMS full scan data can be matched to standards to aid the identification of unknown analytes. The peak capacity for features detected in human urine using LC-FAIMS-MS was increased approximately threefold compared to LC-MS alone due to a combination of the reduction of chemical noise and separation of coeluting isobaric species across the entire analytical space. The use of FAIMS-selected in source collision induced dissociation (FISCID) yields fragmentation of ions, which reduces sample complexity associated with overlapping fragmentation patterns and provides structural information on the selected precursor ions

High throughput volatile fatty acid skin metabolite profiling by thermal desorption secondary electrospray ionisation mass spectrometry

The non-invasive nature of volatile organic compound (VOC) sampling from skin makes this a priority in the development of new screening and diagnostic assays. Evaluation of recent literature highlights the tension between the analytical utility of ambient ionisation approaches for skin profiling and the practicality of undertaking larger campaigns (higher statistical power), or undertaking research in remote locations. This study describes how VOC may be sampled from skin and recovered from a polydimethylsilicone sampling coupon and analysed by thermal desorption (TD) interfaced to secondary electrospray ionisation (SESI) time-of-flight mass spectrometry (MS) for the high throughput screening of volatile fatty acids (VFAs) from human skin. Analysis times were reduced by 79% compared to gas chromatography-mass spectrometry methods (GC-MS) and limits of detection in the range 300 to 900 pg cm−2 for VFA skin concentrations were obtained. Using body odour as a surrogate model for clinical testing 10 Filipino participants, 5 high and 5 low odour, were sampled in Manilla and the samples returned to the UK and screened by TD-SESI-MS and TD-GC-MS for malodour precursors with greater than >95% agreement between the two analytical techniques. Eight additional VFAs were also identified by both techniques with chains 4 to 15 carbons long being observed. TD-SESI-MS appears to have significant potential for the high throughput targeted screening of volatile biomarkers in human skin

Characterization of crude oil and its saturate, aromatic and resin fractions by high-field asymmetric waveform ion mobility spectrometry – high resolution mass spectrometry

High-field asymmetric waveform ion mobility spectrometry (FAIMS) was coupled to a high-resolution Orbitrap mass spectrometer (MS) with a heated electrospray ionization (HESI) source for the analysis of crude oil and respective saturate, aromatic, and resin fractions. Four classes of compounds N1, N1S1, O1S1, and O2S1 were investigated using FAIMS one-dimensional compensation field scans from −3 to 5 Td for the crude oil and FAIMS static scans from 0.5 to 2.5 Td with 0.5 Td increments for fractions. In all cases, the incorporation of FAIMS into the analysis resulted in an increased number of detected peaks for both the crude oil and fractions. The most significant change was noticed in the aromatic fraction, with an increase of 218% for N1 and up to 514% for the O2S1 class of compounds observed. In addition, pre-analytical fractionation combined with FAIMS–MS enabled a higher number of molecular features to be observed in comparison to whole oil for three classes of compounds N1, O1S1, and O2S1 by 19, 45, and 83%, respectively

Combined hydrophilic interaction liquid chromatography-scanning field asymmetric waveform ion mobility spectrometry-time-of-flight mass spectrometry for untargeted metabolomics

Untargeted metabolite profiling of biological samples is a challenge for analytical science due to the high degree of complexity of biofluids. Isobaric species may also not be resolved using mass spectrometry alone. As a result of these factors, many potential biomarkers may not be detected or are masked by co-eluting interferences in conventional LC-MS metabolomic analyses. In this study, a comprehensive liquid chromatography-mass spectrometry workflow incorporating a fast-scanning miniaturised high-field asymmetric waveform ion mobility spectrometry separation (LC-FAIMS-MS) is applied to the untargeted metabolomic analysis of human urine. The time-of-flight mass spectrometer used in the study was scanned at a rate of 20 scans s−1 enabling a FAIMS CF spectrum to be acquired within a 1-s scan time, maintaining an adequate number of data points across each LC peak. The developed method is demonstrated to be able to resolve co-eluting isomeric species and shows good reproducibility (%RSD < 4.9%). The nested datasets obtained for fresh, aged, and QC urine samples were submitted for multivariate statistical analysis. Seventy unique biomarker ions showing a statistically significant difference between fresh and aged urine were identified with optimal transmission CF values obtained across the full CF spectrum. The potential of using FAIMS to select ions for in-source collision-induced dissociation is demonstrated for FAIMS-selected methylxanthine ions yielding characteristic fragment ion species indicative of the precursor

The quantitative surface analysis of an antioxidant additive in a lubricant oil matrix by desorption electrospray ionization mass spectrometry

Rationale Chemical additives are incorporated into commercial lubricant oils to modify the physical and chemical properties of the lubricant. The quantitative analysis of additives in oil-based lubricants deposited on a surface without extraction of the sample from the surface presents a challenge. The potential of desorption electrospray ionization mass spectrometry (DESI-MS) for the quantitative surface analysis of an oil additive in a complex oil lubricant matrix without sample extraction has been evaluated. Methods The quantitative surface analysis of the antioxidant additive octyl (4-hydroxy-3,5-di-tert-butylphenyl)propionate in an oil lubricant matrix was carried out by DESI-MS in the presence of 2-(pentyloxy)ethyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate as an internal standard. A quadrupole/time-of-flight mass spectrometer fitted with an in-house modified ion source enabling non-proximal DESI-MS was used for the analyses. RESULTS An eight-point calibration curve ranging from 1 to 80 μg/spot of octyl (4-hydroxy-3,5-di-tert-butylphenyl)propionate in an oil lubricant matrix and in the presence of the internal standard was used to determine the quantitative response of the DESI-MS method. The sensitivity and repeatability of the technique were assessed by conducting replicate analyses at each concentration. The limit of detection was determined to be 11 ng/mm additive on spot with relative standard deviations in the range 3-14%. CONCLUSIONS The application of DESI-MS to the direct, quantitative surface analysis of a commercial lubricant additive in a native oil lubricant matrix is demonstrated

Direct determination of urinary creatinine by reactive-thermal desorption-extractive electrospray-ion mobility-tandem mass spectrometry.

A direct, ambient ionization method has been developed for the determination of creatinine in urine that combines derivatization and thermal desorption with extractive electrospray ionization and ion mobility-mass spectrometry. The volatility of creatinine was enhanced by a rapid on-probe aqueous acylation reaction, using a custom-made thermal desorption probe, allowing thermal desorption and ionization of the monoacylated derivative. The monoacyl creatinine [M + H] ion (m/z 156) was subjected to mass-to-charge selection and collision induced dissociation to remove the acyl group, generating the protonated creatinine [M + H] product ion at m/z 114 before an ion mobility separation was applied to reduce chemical noise. Stable isotope dilution using creatinine-d as internal standard was used for quantitative measurements. The direct on-probe derivatization allows high sample throughput with a typical cycle time of 1 min per sample. The method shows good linearity (R = 0.986) and repeatability (%RSD 8-10%) in the range of 0.25-2.0 mg/mL. The creatinine concentrations in diluted urine samples from a healthy individual were determined to contain a mean concentration of 1.44 mg/mL creatinine with a precision (%RSD) of 9.9%. The reactive ambient ionization approach demonstrated here has potential for the determination of involatile analytes in urine and other biofluids. © 2013 American Chemical Society

Determination of free desmosine and isodesmosine as urinary biomarkers of lung disorder by ultra performance liquid chromatography-ion mobility-mass spectrometry

The elastin degradation products, desmosine (DES) and isodesmosine (IDES) are highly stable, cross-linking amino-acids that are unique to mature elastin. The excretion of DES/IDES in urine, in the free form and with associated peptide fragments, provides an indicator of lung damage in chronic obstructive pulmonary disease (COPD). A quantitative ion mobility-mass spectrometry (IM-MS) method has been developed for the analysis of free DES/IDES in urine with deuterated IDES as an internal standard. Resolution of DES/IDES isomers was achieved in less than five minutes using ultra performance liquid chromatography (UPLC) combined with ion pairing. The optimized UPLC-IM-MS method provided a linear dynamic range of 10-300 ng/mL and a limit of quantitation of 0.028 ng/mL for IDES and 0.03 ng/mL for DES (0.55 ng and 0.61 ng on column respectively). The method reproducibility (%RSD) was < 4% for DES and IDES. The UPLC-IM-MS method was applied to the analysis of urine samples obtained from healthy volunteers and COPD patients. The DES/IDES concentrations in healthy and COPD urine showed an increase in DES (79%) and IDES (74%) in the COPD samples, relative to healthy controls. The incorporation of an IM separation prior to m/z measurement by MS was shown to reduce non-target ion responses from the bio-fluid matrix

The determination of salivary oxypurines before and after exercise by combined liquid chromatography-field asymmetric waveform ion mobility spectrometry-time-of-flight mass spectrometry

© 2018 Springer-Verlag GmbH Germany, part of Springer Nature A method combining field asymmetric waveform ion mobility spectrometry with liquid chromatography-mass spectrometry (LC-FAIMS-MS) has been developed for the analysis of the oxypurine compounds hypoxanthine (HX) and xanthine (XA) in saliva. Separation of the oxypurines from interfering matrix components was investigated using FAIMS-MS. The selected FAIMS parameters were then applied to the rapid LC-FAIMS-MS analysis of HX and XA using a short chromatographic separation method (7 min). A comparison of the LC-MS method with and without FAIMS applied, resulted in improved discrimination from saliva matrix interferences and improved chromatographic peak integration for both HX and XA using a FAIMS separation. A quantitative evaluation of the LC-FAIMS-MS method was performed giving limits of detection of 2.0 ng mL −1 for HX and 1.8 ng mL −1 for XA, and limits of quantification of 6.6 ng mL −1 for HX and 6.0 ng mL −1 for XA. The developed LC-FAIMS-MS method was applied to the targeted analysis of the oxypurine metabolites in saliva collected from healthy male athletes (n = 11) before and after exercise designed to induce oxidative stress; post-exercise collection time-points included immediately after exercise, one hour and twenty-four hours’ post-exercise. The salivary concentrations of both HX and XA were lower after physical exercise, compared to the pre-exercise (rest) concentrations and returned to approximately pre-exercise levels after twenty-four hours. The method reported has the potential for monitoring the salivary oxypurines, HX and XA, as biomarkers of oxidative stress and in other clinical applications