Atmospheric Pressure Chemical Ionization Source Research Articles

Molecular characteristics of eight lignites based on the big data obtained from Orbitrap mass spectrometry

Eight lignites from different regions were selected for thermal dissolution (TD) sequentially using cyclohexane, methanol and ethanol. The TD extracts of the eight coal samples were characterized using atmospheric pressure chemical ionization source (APCI)-Orbitrap mass spectrometry (MS). Chemometric methods were employed to deeply explore the molecular structural and composition information of the organic compounds detected by Orbitrap MS. The longest distance method in systematic clustering of chemometrics was employed to ascertain the optimal number of groups, which was found to be 7 by clustering 24 soluble portions (SPs) using Euclidean distance. Taking one group as an example, the similarities and differences of SPs within the group were derived based on the compositional class of O1N1, N1, O2N1 and O2, and heteroatom distribution patterns of the SPs were proposed and compared. The integration of high-resolution MS data and chemometric methods not only exposes the existence of heteroatomic compounds in lignite but also furnishes evidence for the origin and evolution of lignite, as well as a methodology for the high-value utilization of lignites from different sources.

Structural Assignment of the Product Ion Generated from a Natural Ciguatoxin-3C Congener, 51-Hydroxyciguatoxin-3C, and Discovery of Distinguishable Signals in Congeners Bearing the 51-Hydroxy Group.

Ciguatoxins (CTXs) stand as the primary toxins causing ciguatera fish poisoning (CFP) and are essential compounds distinguished by their characteristic polycyclic ether structure. In a previous report, we identified the structures of product ions generated via homolytic fragmentation by assuming three charge sites in the mass spectrometry (MS)/MS spectrum of ciguatoxin-3C (CTX3C) using LC-MS. This study aims to elucidate the homolytic fragmentation of a ciguatoxin-3C congener. We assigned detailed structures of the product ions in the MS/MS spectrum of a naturally occurring ciguatoxin-3C congener, 51-hydroxyciguatoxin-3C (51-hydoxyCTX3C), employing liquid chromatography/quadrupole time-of-flight mass spectrometry with an atmospheric pressure chemical ionization (APCI) source. The introduction of a hydroxy substituent on C51 induced different fragmentation pathways, including a novel cleavage mechanism of the M ring involving the elimination of 51-OH and the formation of enol ether. Consequently, new cleavage patterns generated product ions at m/z 979 (C55H79O15), 439 (C24H39O7), 149 (C10H13O), 135 (C9H11O), and 115 (C6H11O2). Additionally, characteristic product ions were observed at m/z 509 (C28H45O8), 491 (C28H43O7), 481 (C26H41O8), 463 (C26H39O7), 439 (C24H39O7), 421 (C24H37O6), 171 (C9H15O3), 153 (C9H13O2), 141 (C8H13O2), and 123 (C8H11O).

A new stability indicating HPLC and LC-APCI-MS methods for the estimation of Flucytosine in pharmaceutical dosage forms

Flucytosine is an anti-fungal agent which acts against mycotic infections. The anti-mycotic activity of Flucytosine is due to its conversion in to 5-fluoro uracil. In the present study the authors have proposed a new stability indicating isocratic RP-HPLC as well as LC-APCI-MS methods for the estimation of Flucytosine and the methods are validated as per ICH guidelines. Thermo scientific - TSQ Quantis with Vanquish HPLC coupled with MS was employed for the study with Simpack C18 (250 mm x 4.6 mm x 5µm) column. A triple quadrupole mass spectrometer with atmospheric pressure chemical ionization (APCI) source, running in the positive mode (as well as negative mode) was used for the detection. A mixture of 0.1% Acetic acid: Methanol was used as mobile phase (50:50, v/v) (UV detection at 235 nm). A wide linearity concentration range 1.0-120 μg/ml was observed and the method is found to be precise and accurate and can be used for the estimation of marketed formulations. Stress degradation studies were performed and the method is found to be selective and specific.

Evolution of chlorinated paraffin and olefin fingerprints in sewage sludge from 1993 to 2020 of a Swiss municipal wastewater treatment plant

Exposure of humans to chlorinated paraffins (CPs) and chlorinated olefins (COs) can occur via contact with CP-containing plastic materials. Such plastic materials can contain short-chain CPs (SCCPs), which are regulated as persistent organic pollutants (POPs) under the Stockholm Convention since 2017. Municipal wastewater treatment plants (WWTP) collect effluents of thousands of households and their sludge is a marker for CP exposure. We investigated digested sewage sludge collected in the years 1993, 2002, 2007, 2012, and 2020 from a Swiss WWTP serving between 20000 and 23000 inhabitants. A liquid chromatography mass spectrometry (R > 100000) method, in combination with an atmospheric pressure chemical ionization source (LC-APCI-MS), was used to detect mass spectra of CPs and olefinic side products. A R-based automated spectra evaluation routine (RASER) was applied to search for ∼23000 ions whereof ∼6000 ions could be assigned to CPs, chlorinated mono- (COs), di- (CdiOs) and tri-olefins (CtriOs). Up to 230 CP-, 120 CO-, 50 CdiO- and 20 CtriO-homologues could be identified in sludge. Characteristic fingerprints were deduced describing C- and Cl-homologue distributions, chlorine- (nCl) and carbon- (nC) numbers of CPs and COs. In addition, proportions of saturated and unsaturated material were determined together with proportions of different chain length classes including short- (SC), medium- (MC), long- (LC) and very long-chain (vLC) material. A substantial reduction of SCCPs of 84% was observed from 1993 to 2020. Respective levels of MCCPs, LCCPs and vLCCPs decreased by 61, 69 and 58%. These trends confirm that banned SCCPs and non-regulated CPs are present in WWTP sludge and higher-chlorinated SCCPs were replaced by lower chlorinated MCCPs. Combining high-resolution mass spectrometry with a selective and fast data evaluation method can produce characteristic fingerprints of sewage sludge describing the long-term trends in a WWTP catchment area.

A fast energized dispersive guided extraction of polycyclic aromatic hydrocarbons for risk-based seafood monitoring after an oil spill

After the 2019 oil spill disaster on the Brazilian coast, the demand for polycyclic aromatic hydrocarbons (PAH) analysis in seafood samples increased. The aim of this study was to develop an advanced method of energized dispersive guided extraction (EDGE) and quantification of PAH by liquid chromatography coupled to tandem mass spectrometry with atmospheric-pressure chemical ionization source (LC-APCI-MS/MS). The developed method was validated in terms of selectivity, working range (1.25 – 20.0 µg kg−1), matrix effect (relative errors > 20%, precision (CV < 30%), accuracy (77 – 128%), limits of detection (0.9 – 1.25 µg kg−1) and quantification (1.25 – 5.00 µg kg−1), and decision limit (2.9 – 7.8 µg kg−1). This method was applied to 238 samples to consolidate the first official Brazilian monitoring of PAH in seafood. PAH were quantified in 15% of samples, with concentrations up to 69.3 µg kg−1. The carcinogenic compound B[a]P was present in 4% of samples, with concentrations up to 42.7 µg kg−1. The health risk of seafood consumers was assessed using the margin of exposure (MOE) approach. Despite this, the risk assessment indicated that the disaster was of low concern to human health (MOE > 10.000). This new method increased laboratory throughput and was successfully applied to different types of samples, supporting monitoring of seafood after the disaster.

Mass Specthoscope: A Hand-held Extendable Probe for Localized Noninvasive Sampling of Skin Volatome for Online Analysis.

Human skin emits a unique set of volatile organic compounds (VOCs). These VOCs can be probed in order to obtain physiological information about the individuals. However, extracting the VOCs that emanate from human skin for analysis is troublesome and time-consuming. Therefore, we have developed "Mass Specthoscope"─a convenient tool for rapid sampling and detecting VOCs emitted by human skin. The hand-held probe with a pressurized tip and wireless button enables sampling VOCs from surfaces and their transfer to the atmospheric pressure chemical ionization source of quadrupole time-of-flight mass spectrometer. The system was characterized using chemical standards (acetone, benzaldehyde, sulcatone, α-pinene, and decanal). The limits of detection are in the range from 2.25 × 10-5 to 3.79 × 10-5 mol m-2. The system was initially tested by detecting VOCs emanating from porcine skin spiked with VOCs as well as unspiked fresh and spoiled ham. In the main test, the skin of nine healthy participants was probed with the Mass Specthoscope. The sampling regions included the armpit, forearm, and forehead. Numerous skin-related VOC signals were detected. In the final test, one participant ingested a fenugreek drink, and the participant's skin surface was probed using the Mass Specthoscope hourly during the 8 h period. The result revealed a gradual release of fenugreek-related VOCs from the skin. We believe that this analytical approach has the potential to be used in metabolomic studies and following further identification of disease biomarkers─also in noninvasive diagnostics.

Assignment of product ions produced from ciguatoxin-3C provides a deep insight into the fragmentation mechanism of polycyclic ether compounds.

Marine polycyclic ethers have drawn attention owing to their unique chemical structures and involvement in food poisoning and fish killing. To study structural diversity, we performed a structural assignment of product ions produced from a representative ladder-shaped polycyclic ether, ciguatoxin-3C, and elucidated the mechanism of generation. The product ions used for the structural assignment were produced from a precursor ion [M + H]+ using liquid chromatography/quadrupole time-of-flight mass spectrometry, by employing an atmospheric pressure chemical ionization source. Three charged sites were considered at both terminals of a molecule. Typical charge-remote fragmentation was produced at the respective charge sites, yielding a hybrid spectrum. C-C bonds bordering two ethers could cleave and trigger the fission of two other bonds. Prominent ions indicating the serial loss of water molecules resulted from the simultaneous deprivation of ethereal oxygen and hydrogen atoms. The resultant double bonds formed long chains of conjugated polyenes, which stabilized charge via resonance. Three alternative charge sites produce a hybrid spectrum. The simultaneous fission of three bonds was explained. For the first time, intense ions due to serial dehydration were explained by the elimination of ether oxygen atoms and the subsequent conjugation of double bonds. All product ions were considered by the structural features of polycyclic ether that facilitates the formation of conjugated polyenes.

Method development and validation of a new stability indicating HPLC and LC-APCI-MS methods for the determination of Bumetanide

Bumetanide is a diuretic used to reduce edema caused by the conditions such as heart failure, kidney disease, and liver disease. A new stability indicating isocratic LC-APCI-MS and RP-HPLC methods have been developed and validated for the estimation of Bumetanide as per ICH guidelines. Thermo scientific-TSQ Quantis with Vanquish HPLC coupled with MS was used for the present study. Simpack C18 column was used for chromatographic resolution and a triple quadrupole mass spectrometer with atmospheric pressure chemical ionization (APCI) source, running in the positive mode (as well as negative mode) was used for detection. A mixture of 0.1% Formic acid: Acetonitrile was used as mobile phase on gradient mode and Acetonitrile was used as diluent. A wide linearity concentration range 5.0-200 μg/ml was shown by the proposed method. The proposed methods are simple, precise, accurate and used to quantify the marketed formulations of Bumetanide. Stress degradation studies were performed and the method is found to be selective and specific.

Structural Elucidations of derivatized Sterols using Electrospray Ionization/Atmospheric Pressure Chemical Ionization-Quadrupole Ion Trap-Mass spectrometry

Free sterols are neutral molecules that are difficult to ionize by Electrospray Ionization (ESI) or Atmospheric Pressure Chemical Ionization (APCI). Therefore, in order to increase their ionization efficiency, sterols were converted into their corresponding picolinyl esters. In this study we examined the possibility of analyzing picolinyl ester of sterols derivatives using flow injection ESI-quadrupole ion trap (QIT) MS and APCI-QIT MS and we investigated their fragmentation pathways using low energy collision induced dissociation-tandem mass spectrometry (CID-MS2). This study also aimed to examine the possibility of using ESI-QIT MS3 to identify sterol isomers. The picolinyl esters readily formed protonated molecular ions ([M+H]+) in ESI and APCI sources except for the picolinyl ester of 7-dehydrocholesterol which was detected as the radical cation ion [M].+ using APCI-QIT MS. The ester bonds of picolinyl esters cleaved during CID MS2, resulting in diagnostic fragments corresponding to steryl cation moieties [M+H-C6H5NO2]+. The CID MS3 of [M+H]+ → [M+H-C6H5NO2]+ of picolinyl esters was found to be useful for structural elucidation and for distinguishing among steryl isomers.

Fingerprinting of chlorinated paraffins and their transformation products in plastic consumer products

Chlorinated paraffins (CPs) can be classified according to their length as short-chain (SC, C10–C13), medium-chain (MC, C14–C17) and long-chain (LC, C ≥ 18) CPs. Technical CP-mixtures can contain a wide range of carbon- (C-, nC = 10–30) and chlorine- (Cl-, nCl = 3–19) homologues. CPs are high-production volume chemicals (>106 t/y). They are used as flame-retardants, plasticizers and coolant fluids. Due to the persistence, bioaccumulation, long-range environmental transport potential and adverse effects, SCCPs are regulated as persistent organic pollutants (POPs) by the Stockholm Convention. Transformation of CPs can lead to the formation of unsaturated compounds such as chlorinated mono- (CO), di- (CdiO) and tri-olefins (CtriO). Such transformation reactions can occur at different stages of CP manipulation providing characteristic C-/Cl-homologue distributions. All this results in unique patterns that collectively create a fingerprint, which can be distinguished from CP-containing samples. Therefore, CP-fingerprinting can develop into a promising tool for future source apportionment studies and with it, the reduction of environmental burden of CPs and hazards to humans. Herein, CP-containing plastics were studied to establish fingerprints and develop this method. We analyzed four household items by reverse-phase liquid-chromatography coupled with a mass spectrometer with an atmospheric pressure chemical ionization source and an Orbitrap mass analyzer (RP-LC-APCI-Orbitrap-MS) operated at a resolution of 120000 (FWHM at m/z 200). MS-data of different CP-, CO-, CdiO- and CtriO-homologues were efficiently processed with an R-based automatic mass spectra evaluation routine (RASER). From the 16720 ions searched for, up to 4300 ions per sample were assigned to 340 C-/Cl-homologues of CPs and their transformation products. Specific fingerprints were deduced from the C-/Cl-homologues distributions, the carbon- (nC) and chlorine- (nCl) numbers and saturation degree. These fingerprints were compared with the ones obtained by a GC-ECNI-Orbitrap-MS method.

Sensitive method for simultaneous determination of TBBPA and its ten derivatives

Tetrabromobisphenol A (TBBPA) and its derivatives are regarded as new contaminants, raising much attention on their environmental occurrence and fates. However, the sensitive detection of TBBPA and its main derivatives is still a great challenge. This study investigated a sensitive method for simultaneous detection of TBBPA and its ten derivatives using high-performance liquid chromatography coupled with triple quadrupole mass spectrometry (HPLC-MS/MS) with atmospheric pressure chemical ionization (APCI) source. The method exhibited much better performance than previously reported methods. Furthermore, it was successfully applied in determining complicated environmental samples, including sewage sludge, river water and vegetable samples with concentration range from undetected (n.d.) to 25.8 ng g−1 dry weight (dw). For sewage sludge, river water and vegetable samples, the spiking recoveries of TBBPA and its derivatives ranged from 69.6 ± 7.0% to 86.1 ± 12.9%, 69.5 ± 13.9% to 87.5 ± 6.6%, and 68.2 ± 5.6% to 80.2 ± 8.3%, respectively; the accuracy ranged from 94.9 ± 4.6% to 113 ± 5%, 91.9 ± 10.9% to 112 ± 7%, and 92.1 ± 5.1% to 106 ± 6%, and the method quantitative limits ranged from 0.00801 to 0.224 ng g−1 dw, 0.0104–0.253 ng L−1, and 0.00524–0.152 ng g−1 dw, respectively. Moreover, the present manuscript describes for the first time the simultaneous detection of TBBPA and ten derivatives from various environmental samples, providing fundamental work for further research on their environmental occurrences, behaviors and fates.

A new stability indicating HPLC and LC-APCI-MS methods for the estimation of Clofarabine in pharmaceutical dosage forms

Clofarabine is an anti-cancer drug. A new stability indicating isocratic RP-HPLC and LC-APCI-MS methods have been developed and validated for the quantification of Clofarabine as per ICH guidelines. Thermo scientific-TSQ Quantis with Vanquish HPLC coupled with MS was employed for the present study. Simpack C18 column was used for chromatographic resolution and a triple quadrupole mass spectrometer with atmospheric pressure chemical ionization (APCI) source, running in the positive mode (as well as negative mode) was used for detection. A mixture of 0.1% Formic acid: Acetonitrile was used as mobile phase on gradient mode and a mixture of Methanol: Water (50:50, v/v) was used as diluent. A wide linearity concentration range 5.0-150 μg/mL was shown by the proposed method. The proposed methods are simple, precise, and accurate are used to quantify the marketed formulations of Clofarabine. Stress degradation studies were performed and the method is found to be selective and specific.

An economical setup for atmospheric pressure chemical ionization drift tube ion-mobility mass spectrometry

Ion-mobility (IM) separations—performed in conjunction with mass spectrometry (MS)—increase selectivity of MS analyses. However, IM-MS instruments are costly, and many laboratories are only equipped with standard MS instruments without an IM separation stage. Therefore, it is appealing to upgrade the existing mass spectrometers with low-cost IM separation devices. Such devices can be constructed using widely available materials such as printed-circuit boards (PCBs). We demonstrate coupling of an economical PCB-based IM spectrometer (disclosed previously) with a commercial triple quadrupole (QQQ) mass spectrometer. The presented PCB-IM-QQQ-MS system incorporates an atmospheric pressure chemical ionization (APCI) source, drift tube comprising desolvation and drift regions, ion gates, and transfer line to the mass spectrometer. The ion gating is accomplished with the aid of two floated pulsers. The separated ions are divided into packets, which are sequentially introduced to the mass spectrometer. Volatile organic compounds (VOCs) are transferred with the aid of nitrogen gas flow from the sample chamber to the APCI source. The operation of the system has been demonstrated using standard compounds. The limits of detection for 2,4-lutidine, (−)-nicotine, and pyridine are 2.02 × 10−7 M, 1.54 × 10−9 mol, and 4.79 × 10−10 mol, respectively. The system was also used to monitor VOCs emitted from the porcine skin after exposure to nicotine patches, and VOCs released from meat undergoing the spoilage process. We believe this simple APCI-PCB-IM-QQQ-MS platform can be reproduced by others to augment the capabilities of the existing MS instrumentation.

Determination of the Pesticides Ethoprophos and Atrazine in Water by T-Shaped Atmospheric Pressure Chemical Ionization (APCI) Mass Spectrometry (MS)

With the goal of enhancing the low sensitivity of the conventional atmospheric pressure chemical ionization (APCI) source due to the ion divergence, here is reported a T-shaped ion source to improve the sensitivity with a portable mass spectrometer for the rapid determination of the pesticides ethoprophos and atrazine in water. Compared with conventional APCI, the ion source improves the sensitivity for the analytes. The results show that the analysis requires less than 2 s, the limit of detection (LOD) is better than 0.1 and the relative standard deviation (RSD) is 16% at 1, 5, and 25 The recoveries of the analytes are between 80% and 130%, meeting the requirements for rapid pesticide determination in water.

Novel Liquid Chromatography–Tandem Mass Spectrometry Method for Analysis of 102 Pesticides and Five Mycotoxins Regulated by the State of Colorado in Dried Hemp

A novel liquid chromatography–tandem mass spectrometry (LC–MS/MS) method with a dual electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) source was developed for analyzing 102 pesticides and five mycotoxins that are regulated by the state of Colorado in hemp. The limit of quantitation (LOQ) of the 102 pesticides and five mycotoxins met Colorado state action limit requirements for these analytes in a hemp matrix. For this study, 88 out of 102 pesticides and all five mycotoxins were analyzed using LC–MS/MS with an ESI source, whereas the remaining 14 pesticides were determined using LC–MS/MS with an APCI source. A simple, fast, green, and cheap acetonitrile solvent extraction method was used to extract the pesticides and mycotoxins from the hemp matrix with good extraction efficiency in the range of 80–120%. A hemp matrix is challenging and causes matrix effects such as ion suppression or enhancement. We optimized the LC method and added 30 internal standards to reduce and compensate for these matrix effects to obtain method accuracy in the range of 70–120%. The ionization mechanism of nonpolar pesticides (normally analyzed by gas chromatography–tandem mass spectrometry [GC–MS/MS]) with an APCI ion source was elucidated.

Differentiating Toxic and Nontoxic Tricresyl Phosphate Isomers Using Ion–Molecule Reactions with Oxygen

Ortho-substituted isomers of tricresyl phosphates (TCPs) and their toxic metabolites (e.g., CBDP: cresyl saligenin phosphate) can cause neurotoxic effects in humans. When TCP is introduced to an atmospheric pressure chemical ionization source using gas chromatography, radical cations M•+ are formed by charge exchange. The mass spectrum of an ortho-substituted isomer displays two intense peaks that are absent in the spectra of non-ortho-substituted isomers, leading us to propose structure-diagnostic ion-molecule reactions between ions M•+ and oxygen species present in the source. However, the mechanisms of these reactions have not yet been established. In this study, we propose a mechanism and provide support through computational and experimental analyses using density functional theory and cyclic ion mobility-mass spectrometry. The mechanism consists of a multistep reaction starting with the rearrangement of the molecular ion into a distonic isomer followed by an oxidation step and then decomposition into [CBDP-H]+. This proposal is consistent with the results obtained from a series of isotopically labeled analogues. Cyclic ion mobility experiments with a tri-o-cresyl phosphate standard reveal the presence of at least two hydrogen shift isomers of the product ion [CBDP-H]+ that are connected by a low-lying barrier. The selectivity of the ion-molecule reactions toward ortho-substituted cresyl TCP isomers provides us with an identification tool that can select potentially neurotoxic triaryl phosphate esters present in complex mixtures that are produced in large volume by industry.

Gas Dynamic Virtual Nozzle Sprayer for an Introduction of Liquid Samples in Atmospheric Pressure Ionization Mass Spectrometry.

Electrospray may exhibit inadequate ionization efficiency in some applications. In such cases, atmospheric-pressure chemical ionization (APCI) and photoionization (APPI) can be used. Despite a wide application potential, no APCI and APPI sources dedicated to very low sample flow rates exist on the market. Since the ion source performance depends on the transfer of analytes from the liquid to the gas phase, a nebulizer is a critical component of an ion source. Here, we report on the nebulizer with a gas dynamic virtual nozzle (GDVN) and its applicability in APCI at microliter-per-minute flow rates. Nebulizers differing by geometrical parameters were fabricated and characterized regarding the jet breakup regime, droplet size, droplet velocity, and spray angle for liquid flow rates of 0.75-15.0 μL/min. A micro-APCI source with the GDVN nebulizer behaved as a mass-flow-sensitive detector and provided stable and intense analyte signals. Compared to a classical APCI source, an order of magnitude lower detection limit for verapamil was achieved. Mass spectra recorded with the nebulizer in dripping and jetting modes were almost identical and did not differ from normal APCI spectra. Clogging never occurred during the experiments, indicating the high robustness of the nebulizer. Low-flow-rate APCI and APPI sources with a GDVN sprayer promise new applications for low- and medium-polar analytes.

Development of a sensitive LC-APCI-MS/MS method for simultaneous determination of eleven nitrosamines in valsartan and irbesartan with a simple extraction approach

Nitrosamines (NAs) are potent genotoxic agents (GAs) in several animal species, and some are classified as probable or possible human carcinogens by the International Agency for Research on Cancer (IARC). In July 2018, angiotensin II receptor blockers (ARBs) which are used to treat high blood pressure have been recalled owing to contamination with NAs. In this study, a simple and sensitive method for the determination of eleven NAs in a single analysis was developed, using atmospheric pressure chemical ionisation source coupled liquid chromatography tandem mass spectrometer (LC-APCI-MS/MS). By performing the 17 min-run in dynamic multiple reaction monitoring (dMRM) mode, eleven NAs were separated on a Poroshell HPH C18 (4.6 × 150 mm, 2.7 µm) column with gradient elution implementing mobile phase A consisting of 0.2 % formic acid in water and mobile phase B consisting of methanol. The developed analytical method was successfully applied in both active pharmaceutical ingredients (APIs) and finished products (FPs) of valsartan and irbesartan with straightforward and effective extraction procedures. Good linearity with a correlation coefficient (R2) > 0.996 was achieved over the concentration in a range of 0.5–50 ng/mL. The limits of detection (LODs) ranged in 0.001–0.008 ppm and limits of quantitation (LOQs) ranged in 0.008–0.05 ppm of the method fulfilled thresholds of US Food and Drug Administration (US-FDA) and European Medicines Agency (EMA) for testing of GAs in valsartan and irbesartan. The accuracy of the proposed method ranged from 73.1 % to 115.2 % for APIs and the relative standard deviation (RSD %) was ≤11.3 while these validation parameters were in the range of 80.2–128.5 % and ≤ 10.6 for FPs, respectively.

Insight into the Compositional Features of Organic Matter in Xilinguole Lignite through Two Mass Spectrometers.

Ethanolysis of lignite is an effective approach for converting organic matter of lignite to liquid coal derivatives. Xilinguole lignite (XL) was reacted with ethanol at 320 °C. Then ethanol and isometric carbon disulfide/acetone mixture were used to extract the reaction mixture in a modified Soxhlet extractor to afford extractable portion 1 (EP1) and extractable portion 2 (EP2), respectively. According to analysis of EP1 with a gas chromatography/mass spectrometer, phenolic compounds made up more than 33% of the compounds detected. This could be ascribed to the ethanolysis of XL; that is, ethanol could selectively break the Calkyl-O bonds in lignite, producing more phenolic compounds. Furthermore, a quadrupole Orbitrap mass spectrometer equipped with an atmospheric pressure chemical ionization source was used for comprehensive analysis of the compositional features of EP1. The analysis indicated that O1-3, N1O0-2, and N2S1O3-6 were predominant class species in EP1. Nitrogen atoms in NO-containing organic compounds may exist in the form of pyridine or amidogen, while oxygen atoms primarily exist in furan, alkoxy, carbonyl, and ester groups. In addition, possible chemical structures of NO-containing organic compounds were speculated.

Determination of Genotoxic Impurity N-Nitroso-N-methyl-4-aminobutyric Acid in Four Sartan Substances through Using Liquid Chromatography-Tandem Mass Spectrometry.

N-nitroso-N-methyl-4-aminobutyric acid (NMBA) is the third N-nitrosamine impurity found in sartans. Herein, a sensitive and stable LC-MS/MS method with multiple reactions monitoring mode has been developed for the quantitative determination of NMBA in four sartan substances. The effective separation of NMBA and sartan substances was achieved on a C18 column under gradient elution conditions. The mass spectrometry method of the atmospheric pressure chemical ionization source and internal standard method was selected as the quantitative analysis method of NMBA. Then, this proposed LC-MS/MS analysis method was validated in terms of specificity, sensitivity, linearity, accuracy, precision and stability. Good linearity with correlation coefficient over 0.99 was obtained at the NMBA concentration of 3-45 ng/mL, and the limit of quantification was 3 ng/mL. Additionally, the recoveries of NMBA in four sartan substances ranged from 89.9% to 115.7%. The intra-day and inter-day relative standard deviation values were less than 5.0%. In conclusion, this developed determination method for NMBA through liquid chromatography-tandem mass spectrometry showed the characteristics of good sensitivity, high accuracy and precision, which will be of great help for the quantitative analysis of NMBA in sartan products.