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Fast eruption desorption ionization (FEDI) technique was developed for simple, rapid, and sensitive analysis of various compounds. The FEDI allows three analytical modes each with the unique characteristic. The results demonstrated that non-assisted eruption was suitable for stable and volatile compounds, energetic material (EM)-assisted for nonvolatile molecules especially metal compounds, and solvent-assisted eruption for fragile molecules. High-quality mass spectra with intact ions of analytes were obtained in positive and negative ion modes.ᅟ [ABSTRACT FROM AUTHOR]

A carbon fiber ionization (CFI) technique was developed for the mass spectrometric analysis of various organic compounds with different polarities. The design of the CFI technique was based on the good compatibility and dispersion of samples and solutions in different solvents on carbon fiber. As a fast, convenient, and versatile ionization method, CFI-MS is especially efficient for analyzing many low/nonpolar organic compounds, such as polycyclic aromatic hydrocarbons, long-chain aliphatic aldehydes, sensitive steroids, terpenoids, and organometallic compounds. Some of these compounds may not be well-analyzed by electrospray ionization or electron ionization mass spectrometry. On the basis of our experimental results, the major ion formation mechanism of CFI-MS was suggested to involve desorption in a steam-distillation-like process, and then, ionization occurred mainly via corona discharge under high voltage. CFI-MS could not only work alone but also be coupled with separation techniques. It works well when coupled with supercritical fluid chromatography (SFC) as well as in the analysis of exhaled human air. The high flexibility and versatility of CFI-MS has extended its applications in many areas, such as fast chemical screening, clinical testing, and forensic analysis. [ABSTRACT FROM AUTHOR]

An increasing number of fluorinated drugs, pesticides, and fine chemicals are now produced and applied, especially those containing polyfluorinated aromatic moieties. However, at present, the extent of literature covering the special mass spectrometric behaviors of these compounds remains limited. Herein, we report an unexpected but also general gas-phase dissociation mode of polyfluorinated aromatics in mass spectrometry: expulsion of difluorocarbene (50-Da neutral loss). Results from accurate mass measurements, tandem mass spectrometric experiments, and density functional theory (DFT) calculations support an intramolecular F-atom “ring-walk” migration mechanism for gas-phase CF 2 loss. Based on an assessment of the electron ionization-mass spectrometry (EI-MS) data of more than 40 polyfluorinated aromatic compounds from the National Institute of Standards and Technology data bank, we generalized on the substitution group effects on the difluorocarbene dissociation process of polyfluorinated aromatic compounds in EI-MS. These studies have enriched our knowledge of the special gas-phase reactivity of polyfluorinated aromatics and will provide valuable information in further analytical research of these compounds by mass spectrometry. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Dried blood spot (DBS) samples on filter paper are surging in popularity as a sampling and storage vehicle for a wide range of clinical and pharmaceutical applications. For example, a DBS sample is collected from every baby born in the province of Ontario, Canada, for quantification of approximately one hundred analytes that are used to screen for 28 conditions, including succinylacetone (SA), a marker for hepatorenal tyrosinemia. Unfortunately, the conventional methods used to evaluate DBS samples for newborn screening and other applications are tedious and slow, with limited options for automated analysis. In response to this challenge, we have developed a method to couple digital microfluidics (DMF) to nanoelectrospray ionization mass spectrometry (nESI-MS) for SA quantification in DBS samples. The new system is formed by sandwiching a pulled glass capillary emitter between the two DMF substrates such that the capillary emitter is immobilized without external seals or gaskets. Moreover, we introduce a new feedback control system that enables high-fidelity droplet manipulation across DBS samples without manual intervention. The system was validated by application to on-chip extraction, derivatization, and analysis of SA and other analytes from DBS samples, with comparable performance to gold-standard methods. We propose that the new methods described here can potentially contribute to a new generation of analytical techniques for quantifying analytes in DBS samples for a wide range of applications. [ABSTRACT FROM AUTHOR]

Abstract: This review focuses on recent applications of matrix-assisted laser desorption ionization-Fourier-transform ion cyclotron resonance mass spectrometry (MALDI-FTICR-MS) in qualitative and quantitative analysis of low molecular weight compounds. The scope of the work includes amino acids, small peptides, mono and oligosaccharides, lipids, metabolic compounds, small molecule phytochemicals from medicinal herbs and even the volatile organic compounds from tobacco. We discuss both direct analysis and analysis following derivatization. In addition we review sample preparation strategies to reduce interferences in the low m/z range and to improve sensitivities by derivatization with charge tags. We also present coupling of head space techniques with MALDI-FTICR-MS. Furthermore, omics analyses based on MALDI-FTICR-MS were also discussed, including proteomics, metabolomics and lipidomics, as well as the relative MS imaging for bio-active low molecular weight compounds. Finally, we discussed the investigations on dissociation/rearrangement processes of low molecular weight compounds by MALDI-FTICR-MS. [Copyright &y& Elsevier]

A selective, fast, and effective enzyme assay based on matrix-assisted laser desorption/ionization Fourier transform mass spectrometry (MALDI-FTMS) for quantifying β-lactamase, an illegal additive in milk products, has been reported. The strengths of the mass spectrometric assay are its response to all substrate and products, simple and direct detection of the conversion of substrate, and facile determination of enzyme activity. Also, MALDI MS is tolerant to many buffer salts and reagents without the requirement of complicated sample pretreatment procedures. In this study, the approach was used to detect the presence of β-lactamases (BLA) in milk samples. The amount of BLA that could be determined in a milk sample is 6 x 10-3 U∙mL-1 by this approach. To test the strategy, it has been applied to the fortified milk (adding a BLA product known as an antimicrobial destroyer). It is then tested whether the pasteurization procedure of the milk process affects the activity of BI.A in milk samples. This study offers a perspective into the utility of MALDI-FTMS as an alternative detection tool for BLA screening in milk. [ABSTRACT FROM AUTHOR]

Tandem mass spectrometry is used to predict the chemical transformations of 2-pyrimidinyloxy-N-arylbenzyl amine derivatives. Compound 1 , N-2-2-4,6- dimethoxypyrimidin-2-yloxy benzylamino phenyl benzamide was selected as a model to present our idea. The CID reactions of protonated 1 include an intramolecular S N 2 reaction and a cyclodehydration reaction. Under in-source CID conditions, deprotonated 1 undergoes a Smiles rearrangement reaction and then dissociates to the ion at m/z 349. Theoretical computations were invoked to shed light on the reaction mechanisms of 1 by the semiempirical PM3 method. These studies of gas-phase reactions show the reactivity of some potential reaction centers in this molecule, which inspired us to explore the solution phase analogous reactions of 1 . Further experiments show that 1 has two analogous reactions in acidic solution: the acid-catalyzed cyclodehydration reaction and the acid-catalyzed Smiles rearrangement reaction. Moreover, 1 undergoes the base-catalyzed Smiles rearrangement under basic conditions. The present study demonstrates that mass spectrometry can play an important role in predicting the chemical solution phase transformations of 2-pyrimidinyloxy-N-arylbenzyl amine derivatives. [Copyright &y& Elsevier]

The gas-phase fragmentation reactions of 2-hydroxybenzyl-N-pyrimidinylamine derivatives (Compounds 1 to 6 ), the O-N-type acid-catalyzed Smiles rearrangement products of 2-pyrimidinyloxy-N-arylbenzylamine derivatives, have been examined via positive ion matrix-assisted laser desorption/ionization (MALDI) infrared multiphoton dissociation (IRMPD) mass spectrometry in FT-ICR MS and via negative ion electrospray ionization (ESI) in-source collision-induced dissociation (CID) mass spectrometry, respectively. The major fragmentation pathway of protonated 1 to 6 gives the F ions under IRMPD; theoretical results show that the retro-Michael reaction channel is more favorable in both thermodynamics and kinetics. This explanation is supported by H/D exchange experiments and the MS/MS experiment of acetylated 1 . Deprotonated 1 to 6 give rise to the solitary E ions (aromatic nitrogen anions) in the negative ion in-source CID; theoretical calculations show that a retro-Michael mechanism is more reasonable than a gas-phase intramolecular nucleophilic displacement (S N 2) mechanism to explain this reaction process. [Copyright &y& Elsevier]

A rapid static headspace-gas chromatography–mass spectrometry (GC–MS) method was used to determine and to identify the volatile compounds in the rhizomes of Rhodiola sachalinensis and Rhodiola sacra. The total ion chromatograms (TIC) of the rhizomes powders of the R. sachalinensis and R. sacra showed their differences in the volatiles compositions. Thirty two volatile compounds in the rhizome of R. sachalinensis were identified; the main volatile compounds are butanal, 2,6,6-trimethyl-2-ethenyltetrahydro-2-pyran, limonene, linalool, geranial, 2-butanal, and 3-butanal. Twenty five volatile compounds in the rhizome of R. sacra were identified with butanal, 3-butanal, 2-butanal, β-pinene, limonene, terpinolene, and linalool. 2,6,6-Trimethyl-2-ethenyltetrahydro-2-pyran was further identified by the MS–MS technique. The applied method not only effectively differentiates the two species of Rhodiolas but also offers a prospective method for the quality control of aromatic medicine plants. [ABSTRACT FROM AUTHOR]

Eriobotrya japonica , a traditional herbal medicine in China and Japan, has long been used to treat chronic bronchitis and coughs. Pentacyclic triterpenoids (PTs), especially ursolic acid (UA), have been found as reversibly and competitively human neutrophil elastase (HNE) inhibitors. However, the limited solubility and poor bioavailability of PTs hinder their clinical use. Crude plant extracts may have a greater activity than isolated constituents of the equivalent dosage. In this study, an Eriobotrya japonica (loquat leaves) extract (triterpenoid composition of loquat leaves, TCLL) with enriched PTs such as UA was prepared. The study aims to compare the HNE inhibitory (HNEI) effect in vitro and the therapeutic effect on acute lung injury (ALI) in vivo between TCLL and UA. An HNEI activity bioassay was performed with Sivelestat sodium hydrate as a positive control. A lipopolysaccharide (LPS)-induced lung inflammatory model was established to evaluate TCLL's therapeutic effect on ALI in vivo. The absorption of UA in TCLL and in UA alone was determined using a Caco-2 cell uptake model and LC-MS. The IC 50 values of TCLL and UA for the HNEI effect were 3.26 ± 0.56 μg/mL and 8.49 ± 0.42 μg/mL (P < 0.01), respectively. TCLL significantly improved the inflammatory cells and inflammatory cytokine production in mice compared with the LPS group (P < 0.05). Additionally, it performed better than the UA alone group (P < 0.05). Moreover, the uptake by Caco-2 cells of UA in TCLL was higher than that in UA alone (P < 0.05). TCLL has a significant HNEI effect in vitro and a therapeutic effect on LPS-induced inflammation in a mouse model. Both the effects are more efficient than UA. Improved absorption of PTs in TCLL may be one explanation for these results. fx1 [ABSTRACT FROM AUTHOR]

Rationale: Deuterium‐labeled organic compounds, reagents, and drugs are widely used in many scientific research fields. Isotopic purity as the feature parameter of deuterated compounds is of great importance. In this article, we used electrospray ionization with high‐resolution mass spectrometry (ESI‐HRMS) to study isotopic purity of deuterium‐labeled organic compounds based on assigning and distinguishing the corresponding H/D (hydrogen–deuterium) isotopolog ions of deuterated compounds. Methods: We systematically considered the specific requirements of accuracy and resolution of ESI‐HRMS when measuring isotopic purity and demonstrated some actual cases using ESI‐HRMS and ultraperformance liquid chromatography (UPLC)‐HRMS. Meanwhile, ESI‐HRMS/MS of deuterated compounds was performed to obtain more information on deuterium‐labeled position characterization. Results: Two isotopic purity calculation methods based on the relative abundance in ESI‐HRMS and UPLC‐HRMS of H/D isotopolog ions (D0–Dn) were compared, which gave consistent isotopic purity values and were in good agreement with the certified isotopic purity values. We further studied and monitored the H/D exchange reaction of ethyl 3‐(4‐bromophenyl)‐3‐oxopropanoate (EBPO) by evaluating the dynamic isotopic purity changes in EBPO‐D2 in the H/D exchange reaction in situ. Conclusion: The isotopic purity characterization methods using ESI‐HRMS discussed in this article have some outstanding advantages: rapid, highly sensitive, very low sample consumption (even below nanogram level), and deuterated solvent‐free. Thus, this low‐impact analytical method requires less time and is cost effective and might have good application potential for in‐situ isotopic purity analysis and for monitoring the H/D exchange reactions. [ABSTRACT FROM AUTHOR]

A high-performance liquid chromatographic method coupled with triple quadrupole mass spectrometry (LC-MS/MS) for the analysis of blonanserin and its active metabolite, N-desethyl blonanserin, in rat plasma has been developed and validated. The biological samples were treated by simple direct protein precipitation before separation on an Agilent Eclipse Plus C18 column (4.6 × 100 mm, 3.5 μm) with a column temperature of 35°C at a flow rate of 0.5 mL/min. The mobile phase A is a mixture of methanol and water (75 : 25, v/v, 5 mM ammonium formate), and the mobile phase B is acetonitrile containing 0.1% formic acid. The ratio of mobile phase A to mobile phase B is 15 : 85. Electrospray ionization (ESI) multiple reaction monitoring modes are used for detection, which are m/z 368.10 ⟶ 296.90 (blonanserin), m/z 340.15 ⟶ 297.05(N-desethyl blonanserin), and m/z 348.15⟶ 302.05 (N-desethyl blonanserin-d8). The linear response range was 0.1–100.0 ng/mL for blonanserin and N-desethyl blonanserin. The lower limit of quantification (LLOQ), calibration curves, carryover, and matrix effects were sufficiently accurate and precise according to the National Medical Products Administration (NMPA) guidelines for bioanalytical method validation. This analytical method was successfully applied in a blonanserin-poloxamer thermosensitive gel pharmacokinetic study in rats. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Acupoint application of cold asthma recipe (CAR) was a traditional Chinese medicine (TCM) method, widely used as an alternative medicine for clinical prevention of the common winter diseases of asthma and bronchitis. Tetrahydropalmatine (THP) was a main active ingredient of CAR extract. The aim of this study is to compare plasma pharmacokinetics and lung distribution of THP between Feishu (FS) acupoint (BL 13) and Non-Feishu (NFS) acupoint application of CAR extract by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Materials and methods: The extract of CAR was topically administrated in FS and NFS acupoint of rats for plasma pharmacokinetics, and topically administrated in FS and NFS acupoint of mice for lung distribution. The plasma and lung homogenates were pretreated by protein precipitation with acetonitrile. Chromatographic separation was performed on an ACQUITY UPLC BEH C18 column with a mobile phase consisted of 0.1% formic acid in acetonitrile and 0.1% formic acid in water. The detection was accomplished by multiple-reaction monitoring (MRM) scanning in the positive electrospray ionization (ESI+) mode. All pharmacokinetic parameters were estimated by non-compartmental analysis. Results: A sensitive, accurate and precise UPLC-MS/MS method was successfully established for determination of THP in 100?L plasma and lung homogenate. The lower limit of quantification (LLOQ) of THP was 0.05ng/mL and 0.072ng/mL, respectively. The pharmacokinetic results manifested that THP was absorbed and eliminated slowly in plasma. Additionally, it was found that there was significantly higher amount of THP absorbed into blood and lung after FS acupoint application compared to NFS acupoint application. Conclusions: Both of the rat plasma pharmacokinetics and mice lung distribution of THP could support that FS acupoint application of CAR extract has greater advantages of absorption into the blood circulation and distribution in target tissue over NFS acupoint application. The results might be helpful in providing a rational explanation for why the TCM chose the acupoint application and elucidating the underlying mechanism of this treatment. [Copyright &y& Elsevier]

Purpose: The purpose of this study was to investigate the potential effects of a meal and grapefruit juice on the pharmacokinetics of blonanserin and its metabolite N-desethyl blonanserin in healthy Chinese volunteers. Methods: This was a single-centre, open-label, fixed-sequence study, where 12 healthy Chinese volunteers received a single dose of 8 mg blonanserin after an overnight fast in period 1 (reference), a high-fat meal during period 2 and with co-administration of 250 mL of grapefruit juice in period 3. The washout period was 7 days. Series of plasma samples were collected after each dose to determine concentrations of blonanserin and its metabolite N-desethyl blonanserin using liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were estimated by non-compartmental analysis and compared between periods by standard average bioequivalence ANOVA. Adverse events were monitored throughout the study. Results: All subjects completed the study. High-fat meals significantly increased blonanserin exposure (AUC) 2.58-fold (90% CI 2.21, 3.02), relative to the reference period. Co-administration of blonanserin with grapefruit juice remarkably prolonged elimination half-life of blonanserin (from 9.7 to 21.4 h) and significantly increased exposures to blonanserin and N-desethyl blonanserin by 5.82-fold (90% CI 4.57, 7.42) and 1.81-fold (90% CI 1.65, 1.98), respectively. Conclusions: These results suggested that blonanserin was largely metabolised in the intestinal tract before becoming systemically available, and both food and grapefruit juice enhanced exposure to blonanserin and N-desethyl blonanserin. Grapefruit juice increased bioavailability and may have reduced systemic clearance of blonanserin. Further intestinal CYP3A4 and hepatic CYP3A4 might be postulated to explain the delayed elimination of blonanserin. Dose adjustment of blonanserin is needed on the basis of co-intake of known strong CYP3A4 inhibitor. Patients taking high-dose blonanserin also need to be cautious about the ingestion of grapefruit juice. [ABSTRACT FROM AUTHOR]