Mass Spectral Properties Research Articles

Measurement of very low-molecular weight metabolites by traveling wave ion mobility and its use in human urine samples

The collision cross-sections (CCS) measurement using ion mobility spectrometry (IMS) in combination with mass spectrometry (MS) offers a great opportunity to increase confidence in metabolite identification. However, owing to the lack of sensitivity and resolution, IMS has an analytical challenge in studying the CCS values of very low-molecular-weight metabolites (VLMs ≤ 250 Da). Here, we describe an analytical method using ultrahigh-performance liquid chromatography (UPLC) coupled to a traveling wave ion mobility-quadrupole-time-of-flight mass spectrometer optimized for the measurement of VLMs in human urine samples. The experimental CCS values, along with mass spectral properties, were reported for the 174 metabolites. The experimental data included the mass-to-charge ratio (m/z), retention time (RT), tandem MS (MS/MS) spectra, and CCS values. Among the studied metabolites, 263 traveling wave ion mobility spectrometry (TWIMS)-derived CCS values (TWCCSN2) were reported for the first time, and more than 70% of these were CCS values of VLMs. The TWCCSN2 values were highly repeatable, with inter-day variations of <1% relative standard deviation (RSD). The developed method revealed excellent TWCCSN2 accuracy with a CCS difference (ΔCCS) within ±2% of the reported drift tube IMS (DTIMS) and TWIMS CCS values. The complexity of the urine matrix did not affect the precision of the method, as evidenced by ΔCCS within ±1.92%. According to the Metabolomics Standards Initiative, 55 urinary metabolites were identified with a confidence level of 1. Among these 55 metabolites, 53 (96%) were VLMs. The larger number of confirmed compounds found in this study was a result of the addition of TWCCSN2 values, which clearly increased metabolite identification confidence.

Mass Accretion, Spectral, and Photometric Properties of T Tauri Stars in Taurus Based on TESS and LAMOST

We present the analysis of 16 classical T Tauri stars (CTTSs) using LAMOST and TESS data, investigating spectral properties, photometric variations, and mass accretion rates. All 16 stars exhibit emissions in Hα lines, from which the average mass accretion rate of 1.76 × 10−9 M ⊙ yr−1 is derived. Two of the stars, DL Tau and Haro 6-13, show mass accretion bursts simultaneously in TESS, ASAS-SN, and/or the ZTF survey. Based on these observations, we find that the mass accretion rates of DL Tau and Haro 6-13 reach their maxima of 2.5 × 10−8 M ⊙ yr−1 and 2 × 10−10 M ⊙ yr−1, respectively, during the TESS observation. We detect 13 flares among these stars. The flare frequency distribution shows that the CTTSs’ flare activity is not only dominated by strong flares with high energy but also much more active than those of solar-type and young low-mass stars. By comparing the variability classes reported in the literature, we find that the transition timescale between different classes of variability in CTTSs, such as from stochastic (S) to bursting (B) or from quasi-periodic symmetric to quasi-periodic dipping, may range from 1.6 to 4 yr. We observe no significant correlation between inclination and mass accretion rates derived from the emission indicators. This suggests that inner disk properties may be more important than those of outer disks. Finally, we find a relatively significant positive correlation between the asymmetric metric M and the cold disk inclination compared to the literature. A weak negative correlation between the periodicity metric Q value and inclination has also been found.

Synthesis and Theoretical Studies of Biologically Active Thieno Nucleus Incorporated Tri and Tetracyclic Nitrogen Containing Heterocyclics Scaffolds via Suzuki Cross-Coupling Reaction.

A new series of thieno nucleus embellished trinuclear (19, 20) and tetranuclear (21-24) nitrogen heteroaryl have been synthesized by the Suzuki cross-coupling reaction using bis(triphenylphosphine)palladium(II) dichloride. All the synthesized compounds were characterized by IR, 1 H-NMR, 13 CNMR and Mass spectral properties. In vitro antibacterial studies of the synthesized compound were conducted using broth microdilution assay employing Gram-positive and Gram-negative strains and half-maximal inhibitory concentration (IC50 ) was determined. The result showed that compound 20 possess best antibacterial activity against S. aureus and E. coli with IC50 values of 60 μg mL-1 and 90 μg mL-1 . Further to determine the mode of antibacterial action, compounds 20 and 21 were examined for in vitro bacterial dehydrogenase inhibitory assay. To understand the binding affinity of the synthesized compounds, the docking study was performed in the bacterial dehydrogenase enzyme by AutoDock Vina software and structure was confirmed by Discovery Studio Visualizer. All the synthesized compounds were docked in a good manner within the active sites of the bacterial dehydrogenase enzyme and exhibited good binding energies.

Probing Early Supermassive Black Hole Growth and Quasar Evolution with Near-infrared Spectroscopy of 37 Reionization-era Quasars at 6.3 &lt; z ≤ 7.64

Abstract We report the results of near-infrared spectroscopic observations of 37 quasars in the redshift range 6.3 &lt; z ≤ 7.64, including 32 quasars at z &gt; 6.5, forming the largest quasar near-infrared spectral sample at this redshift. The spectra, taken with Keck, Gemini, VLT, and Magellan, allow investigations of central black hole mass and quasar rest-frame ultraviolet spectral properties. The black hole masses derived from the Mg ii emission lines are in the range (0.3–3.6) × 109 M ⊙, which requires massive seed black holes with masses ≳103–104 M ⊙, assuming Eddington accretion since z = 30. The Eddington ratio distribution peaks at λ Edd ∼ 0.8 and has a mean of 1.08, suggesting high accretion rates for these quasars. The C iv–Mg ii emission-line velocity differences in our sample show an increase of C iv blueshift toward higher redshift, but the evolutionary trend observed from this sample is weaker than the previous results from smaller samples at similar redshift. The Fe ii/Mg ii flux ratios derived for these quasars up to z = 7.6, compared with previous measurements at different redshifts, do not show any evidence of strong redshift evolution, suggesting metal-enriched environments in these quasars. Using this quasar sample, we create a quasar composite spectrum for z &gt; 6.5 quasars and find no significant redshift evolution of quasar broad emission lines and continuum slope, except for a blueshift of the C iv line. Our sample yields a strong broad absorption line quasar fraction of ∼24%, higher than the fractions in lower-redshift quasar samples, although this could be affected by small sample statistics and selection effects.

Overestimation of 3α- over 3β-25-Hydroxyvitamin D3 Levels in Serum: A Mechanistic Rationale for the Different Mass Spectral Properties of the Vitamin D Epimers.

The metabolism of vitamin D3 includes a parallel C-3 epimerization pathway-in addition to the standard metabolic processes for vitamin D3-reversing the stereochemical configuration of the -OH group at carbon-3 (β→α). While the biological function of the 3α epimer has not been elucidated yet, the additional species cannot be neglected in the analytical determination of vitamin D3, as it has the potential to introduce analytical errors if not properly accounted for. Recently, some inconsistent mass spectral behavior was seen for the 25-hydroxyvitamin D3 (25(OH)D3) epimers during quantification using electrospray LC-MS/MS. The present work extends that of Flynn et al. ( Ann. Clin. Biochem. 2014, 51, 352-559) and van den Ouweland et al. ( J. Chromatogr. B 2014, 967, 195-202), who reported larger electrospray ionization response factors for the 3α epimer of 25(OH)D3 in human serum samples as compared to the regular 3β variant. The present work was concerned with the mechanistic reasons for these differences. We used a combination of electrospray ionization, atmospheric pressure chemical ionization, and density functional theory calculations to uncover structural dissimilarities between the epimers. A plausible mechanism is described based on intramolecular hydrogen bonding in the gas phase, which creates a small difference of proton affinities between the epimers. More importantly, this mechanism allows the explanation of the different ionization efficiencies of the epimers based on kinetic control of the ionization process, where ionization initially takes place at the hydroxyl group with subsequent proton transfer to a basic carbon atom. The barrier for this transfer differs between the epimers and is in direct competition with H2O elimination from the protonated hydroxyl group. The "hidden" site of high gas phase basicity was revealed through computational calculations and appears to be inaccessible via direct protonation.

A targeted ultra performance liquid chromatography – Tandem mass spectrometric assay for tyrosine and metabolites in urine and plasma: Application to the effects of antibiotics on mice

Tyrosine plays a key role in mammalian biochemistry and defects in its metabolism (e.g., tyrosinemia, alkaptonuria etc.) have significant adverse consequences for those affected if left untreated. In addition, gut bacterially-derived p-cresol and its metabolites are of interest as a result of various effects on host xenobiotic metabolism. A fit-for-purpose quantitative ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) assay was developed to target and quantify tyrosine and eleven metabolites in urine and plasma. Dansylation, using dansyl chloride, was used to improve chromatographic and mass spectral properties for tyrosine and nine phenolic metabolites, with detection using positive electrospray ionisation (ESI). The sulfate and glucuronide conjugates of p-cresol, where the phenol group was blocked, were quantified intact, using negative ESI via polarity switching during the same run. Sample preparation for urine and plasma involved deproteinization by solvent precipitation (of acetonitrile:isopropyl alcohol (1:1 v/v)) followed by in situ dansylation in 96 well plates. To minimize sample and solvent usage, and maximize sensitivity, analysis was performed using microbore reversed-phase gradient UPLC on a C8 phase with a 7.5 min. cycle time. The coefficients of variation obtained were <15%, with lower limits of quantification ranging from 5 to 250 nM depending upon the analyte. The method was applied to plasma and urine samples obtained from mice placed on a high tyrosine diet with one subgroup of animals subsequently receiving antibiotics to suppress the gut microbiota. Whilst plasma profiles were largely unaffected by antibiotic treatment clear reductions in the amount of p-cresol sulfate and p-cresol glucuronide excreted in the urine were observed for these mice.

LC/MS Analysis of Cyclo Fatty Acid-containing Triacylglycerols in Cottonseed Oil

We measured the constituent triacylglycerol of cotton oil, the only edible oil containing a cyclo fatty acid. Due to the difficulty of obtaining a standard for triacylglycerols containing cyclo fatty acids, cotton oil is analyzed using cyclo triacylglycerol in kapok oil as a reference. Analytical methods used liquid chromatography fast atom bombardment mass spectrometry (LC / FAB-MS) using a matrix of 3% m-NBA containing 3 mM NaCl, and orthogonal transfer method for APCI / TOF-MS. FAB mass spectral properties of triacylglycerols containing cyclo fatty acids can be observed with [M + Na]+, [M-1]+ molecular ions, and [M- (RCOO)] + fragments. In the orthogonal APCI / TOF-MS spectrum, only the [M-1] + molecular ion appears, so that the presence of triacylglycerol containing CPFA becomes apparent. On the other hand, chain triacylglycerol can be observed as [M + 1]+ molecular ions and [M- (RCOO)]+ fragments. Based on these observations, triacylglycerols containing ten types of cyclo fatty acids were successfully successfully detected in crude cottonseed oil. In addition, the APCI/TOF-MS technique successfully detected dilinoleoyl-marvalyl-glycerol and palmtoyl-linoleoyl-marvalyl glycerol in the purified cottonseed oil.

Alkyl-Dimethylpyrazines in Mandibular Gland Secretions of Four Odontomachus Ant Species (Formicidae: Ponerinae).

Ponerine ants are known to contain mixtures of pyrazines in their mandibular glands. We analyzed the mandibular gland contents of four ponerine species (Odontomachus chelifer, O. erythrocephalus, O. ruginodis, and O. bauri) by gas chromatography coupled with mass spectrometry, and found that each species contains specific mixtures of trisubstituted alkylpyrazines among other volatiles. Attempts to identify alkylpyrazines solely by mass spectral interpretation is unrealistic because spectra of positional isomers are indistinguishable. To avoid misidentifications, we synthesized a large number of reference compounds and compared their mass spectral and gas chromatographic properties with those present in the Odontomachus species under investigation. Most of the compounds identified were 2-alkyl-3,5-dimethylpyrazines. Interestingly, when the third substituent was an isopentyl group, the two methyl groups were found to be located at the 2 and 5 ring positions. Using our data, we recognized several misidentifications in previous publications.

Syntheses, crystal structures, lone pair functionality and electrospray ionization mass spectral properties of trinuclear, dimer of trinuclear and trinuclear-based one-dimensional systems of copper(II) and lead(II)

This work presents the syntheses, crystal structures, lone pair functionality and electrospray ionization spectra in positive mode (ESI-MS positive) of two trinuclear CuIIPbIICuII compounds [(CuIIL1)2PbII(ClO4)2] (1) and [(CuIIL2)2PbII(NO3)2] (2), one dimer of trinuclear (CuIIPbIICuII)2 compound [{(CuIIL2)2PbII}2(μ-adipate)](ClO4)2·2H2O (3) and one trinuclear CuIIPbIICuII–based one-dimensional (1D) compound [(CuIIL2)2PbII(μ1,5-dicyanamide)2]n (4), where H2L1 and H2L2 are the [2+1] condensation products of salicylaldehyde and, respectively, 1,3-diaminopropane and 2,2′-dimethyl-1,3-diaminopropane. The four compounds have been synthesized by treating the corresponding copper(II) metallo-ligand with a PbII salt (for 1 and 2) or with a PbII salt and a secondary bridging ligand (adipic acid for 3 and sodium dicyanamide for 4). In the trinuclear CuIIPbIICuII moiety in all of 1–4, the PbII center resides in between two [CuIIL1]/[CuIIL2] moieties and copper(II) and lead(II) for each of the two CuIIPbII pairs are diphenoxo bridged. Two trinuclear units are interlinked by an adipate to form the dimeric hexanuclear compound 3. The neighbouring trinuclear units are interlinked by two dicyanamides, forming one-dimensional coordination polymer 4. ESI-MS positive spectra reveal the existence of mono/di/trinuclear and even unusual tetranuclear star type gaseous positive ions; the observed and simulated isotopic distribution patterns are nicely matched. The existence of stereochemically active/inactive lone pair of electrons of lead(II) has been explored. Salient and interesting features in the structures and ESI-MS have been discussed.

Synthesis and anticancer activity evaluation of (E)-3-{[5-(aryl)-1,3,4-oxadiazol-2-yl]methyl}-5-(3,4,5-trimethoxybenzylidene)thiazolidine-2,4-diones

A series of new substituted (E)-3-{[5-(aryl)-1,3,4-oxadiazol-2-yl]methyl}-5-(3,4,5-trimethoxy-benzylidene) thiazolidine-2,4-diones have been synthesized. The products have been characterized by their IR, 1H NMR, 13C NMR, and mass spectral properties and evaluated for anticancer activity against four human cancer cell lines: A549, A375, MCF-7, and HT-29.

Calculation of retention time tolerance windows with absolute confidence from shared liquid chromatographic retention data

Compound identification by liquid chromatography–mass spectrometry (LC–MS) is a tedious process, mainly because authentic standards must be run on a user's system to be able to confidently reject a potential identity from its retention time and mass spectral properties. Instead, it would be preferable to use shared retention time/index data to narrow down the identity, but shared data cannot be used to reject candidates with an absolute level of confidence because the data are strongly affected by differences between HPLC systems and experimental conditions. However, a technique called “retention projection” was recently shown to account for many of the differences. In this manuscript, we discuss an approach to calculate appropriate retention time tolerance windows for projected retention times, potentially making it possible to exclude candidates with an absolute level of confidence, without needing to have authentic standards of each candidate on hand. In a range of multi-segment gradients and flow rates run among seven different labs, the new approach calculated tolerance windows that were significantly more appropriate for each retention projection than global tolerance windows calculated for retention projections or linear retention indices. Though there were still some small differences between the labs that evidently were not taken into account, the calculated tolerance windows only needed to be relaxed by 50% to make them appropriate for all labs. Even then, 42% of the tolerance windows calculated in this study without standards were narrower than those required by WADA for positive identification, where standards must be run contemporaneously.

Mass spectrometry-based analysis of whole-grain phytochemicals

ABSTRACTWhole grains are a rich source of several classes of phytochemicals, such as alkylresorcinols, benzoxazinoids, flavonoids, lignans, and phytosterols. A high intake of whole grains has been linked to a reduced risk of some major noncommunicable diseases, and it has been postulated that a complex mixture of phytochemicals works in synergy to generate beneficial health effects. Mass spectrometry, especially when coupled with liquid chromatography, is a widely used method for the analysis of phytochemicals owing to its high sensitivity and dynamic range. In this review, the current knowledge of the mass spectral properties of the most important classes of phytochemicals found in cereals of common wheat, barley, oats, and rye is discussed.

Chemical structure and properties of interstrand cross-links formed by reaction of guanine residues with abasic sites in duplex DNA.

A new type of interstrand cross-link resulting from the reaction of a DNA abasic site with a guanine residue on the opposing strand of the double helix was recently identified, but the chemical connectivity of the cross-link was not rigorously established. The work described here was designed to characterize the chemical structure and properties of dG-AP cross-links generated in duplex DNA. The approach involved characterization of the nucleoside cross-link "remnant" released by enzymatic digestion of DNA duplexes containing the dG-AP cross-link. We first carried out a chemical synthesis and complete spectroscopic structure determination of the putative cross-link remnant 9b composed of a 2-deoxyribose adduct attached to the exocyclic N(2)-amino group of dG. A reduced analogue of the cross-link remnant was also prepared (11b). Liquid chromatography-tandem mass spectrometric (LC-MS/MS) analysis revealed that the retention times and mass spectral properties of synthetic standards 9b and 11b matched those of the authentic cross-link remnants released by enzymatic digestion of duplexes containing the native and reduced dG-AP cross-link, respectively. These results establish the chemical connectivity of the dG-AP cross-link released from duplex DNA and provide a foundation for detection of this lesion in biological samples. The dG-AP cross-link in duplex DNA was remarkably stable, decomposing with a half-life of 22 days at pH 7 and 23 °C. The intrinsic chemical stability of the dG-AP cross-link suggests that this lesion in duplex DNA may have the power to block DNA-processing enzymes involved in transcription and replication.

Identification and characterisation of a novel mono-unsaturated highly branched isoprenoid (HBI) alkene in ancient Arctic sediments

The occurrence of a novel C25 highly branched isoprenoid (HBI) mono-unsaturated hydrocarbon in Arctic marine sediments from the Fram Strait is described. The structure was determined following synthesis from a closely related diene and NMR spectroscopic analysis. The position of the double bond was confirmed by oxidation (RuO4) and comparison of the mass spectrum of the resulting C19 ketone with that of an authentic sample synthesised previously. The same C19 ketone was also present following oxidation of the Fram Strait sediment extracts. The source of the novel HBI monoene biomarker is not known, but is believed to be certain marine diatoms on the basis of structural similarities with other HBIs from such sources. It does not, however, appear to be biosynthesised by Arctic sea ice diatoms, unlike its regio isomer, IP25, an established proxy for Arctic sea ice. Alternatively, it may represent a diagenetic product of the sea ice diatom biomarker IP25; this seems unlikely, however, on the basis of their respective structures. Since the new HBI monoene and IP25 possess similar gas chromatographic and mass spectral properties, but probably have contrasting sources, we suggest that future paleo sea ice reconstruction studies based on the occurrence of IP25 should pay further attention to the rigorous assignment of this biomarker in marine sediment extracts. Some suggestions for achieving this, based on analytical purification and mass spectrometric measurements, are provided.

Identification and analytical properties of acetyl fentanyl metabolites

Acetyl fentanyl is a novel designer drug substance, a derivative of fentanyl. Its major metabolites were identified in samples of urine from consumers of acetyl fentanyl using gas chromatography and high-performance liquid chromatography with mass spectrometry detection. Structures of metabolites were proposed and confirmed by their fragmentation on electron impact and atmospheric pressure chemical ionization. The mass spectral and chromatographic properties of some derivatives of acetyl fentanyl metabolites were determined. The main path of the biotransformation of acetyl fentanyl is the hydroxylation of the phenylethyl moiety in the molecule.

Hydrocarbon Group-Type Analysis of Petroleum-Derived and Synthetic Fuels Using Two-Dimensional Gas Chromatography

A group-type analysis of hydrocarbons in a complex jet fuel may be more useful than attempting to analyze every component because the latter inevitably leaves a large portion of the fuel unidentified. While it may be difficult to accurately determine the identity of a particular compound, that compound can often be classified as belonging to a group or compound class because of its chromatographic retention and mass spectral properties. Compound class quantitation is often capable of relating compositional information to fuel properties. Two-dimensional gas chromatography (GC × GC) is a technique capable of providing this group-type separation and quantitation in jet fuels. This technique was used to examine a large set of fuels (Jet A, Jet A-1, JP-5, and JP-8, primarily) from petroleum sources and non-petroleum alternative sources, such as synthetic paraffinic kerosene (SPK). By comparing results from GC × GC analysis to established techniques and model compound studies, we have found that the accuracy of GC × GC for group-type analysis is excellent. Quantitation of group types for alternative fuel sources were also investigated and compared to conventional techniques. The possible uses and applications of group-type measurements using GC × GC for fuels and fuel-related materials are discussed.

Synthesis and Characterization of Arsenolipids: Naturally Occurring Arsenic Compounds in Fish and Algae.

Arsenic-containing lipids (arsenolipids) are natural products present in fish and algae. Because these compounds occur in foods, there is considerable interest in their human toxicology. We report the synthesis and characterization of seven arsenic-containing lipids, including six natural products. The compounds comprise dimethylarsinyl groups attached to saturated long-chain hydrocarbons (three compounds), saturated long-chain fatty acids (two compounds), and monounsaturated long chain fatty acids (two compounds). The arsenic group was introduced through sodium dimethylarsenide or bis(dimethylarsenic) oxide. The latter route provided higher and more reproducible yields, and consequently, this pathway was followed to synthesize six of the seven compounds. Mass spectral properties are described to assist in the identification of these compounds in natural samples. The pure synthesized arsenolipids will be used for in vitro experiments with human cells to test their uptake, biotransformation, and possible toxic effects.

Demonstration of the Innate Electrophilicity of 4-(3-(Benzyloxy)phenyl)-2-(ethylsulfinyl)-6-(trifluoromethyl)pyrimidine (BETP), a Small-Molecule Positive Allosteric Modulator of the Glucagon-Like Peptide-1 Receptor

4-(3-(Benzyloxy)phenyl)-2-(ethylsulfinyl)-6-(trifluoromethyl)pyrimidine (BETP) represents a novel small-molecule activator of the glucagon-like peptide-1 receptor (GLP-1R), and exhibits glucose-dependent insulin secretion in rats following i.v. (but not oral) administration. To explore the quantitative pharmacology associated with GLP-1R agonism in preclinical species, the in vivo pharmacokinetics of BETP were examined in rats after i.v. and oral dosing. Failure to detect BETP in circulation after oral administration of a 10-mg/kg dose in rats was consistent with the lack of an insulinotropic effect of orally administered BETP in this species. Likewise, systemic concentrations of BETP in the rat upon i.v. administration (1 mg/kg) were minimal (and sporadic). In vitro incubations in bovine serum albumin, plasma, and liver microsomes from rodents and humans indicated a facile degradation of BETP. Failure to detect metabolites in plasma and liver microsomal incubations in the absence of NADP was suggestive of a covalent interaction between BETP and a protein amino acid residue(s) in these matrices. Incubations of BETP with glutathione (GSH) in buffer revealed a rapid nucleophilic displacement of the ethylsulfoxide functionality by GSH to yield adduct M1, which indicated that BETP was intrinsically electrophilic. The structure of M1 was unambiguously identified by comparison of its chromatographic and mass spectral properties with an authentic standard. The GSH conjugate of BETP was also characterized in NADPH- and GSH-supplemented liver microsomes and in plasma samples from the pharmacokinetic studies. Unlike BETP, M1 was inactive as an allosteric modulator of the GLP-1R.

(S)‐(−)‐N‐(Pentafluorobenzylcarbamoyl)prolyl chloride: a chiral derivatisation reagent designed for gas chromatography/negative ion chemical ionisation mass spectrometry of amino compounds

The synthesis of a novel chiral derivatisation reagent, (S)-(-)-N-(pentafluorobenzylcarbamoyl)prolyl chloride is described which is preferably useful for negative-ion chemical ionisation mass spectrometry. Preparation of the reagent followed a general strategy used to prepare enantioselective reagents based on the N-substitution of L-proline. Pentafluorobenzyl chloroformate smoothly reacted with L-proline to give the desired derivatisation reagent after conversion into the acyl chloride. The product was sufficiently pure to be used in the following steps without any additional purification. The reagent was tested against selected chiral and non-chiral analytical targets. Chromatographic enantioseparation was at least equal to the commonly used (S)-(-)-N-(heptafluorobutyryl)prolyl derivatives. The derivatives exhibit excellent mass spectral properties under negative ion chemical ionisation, i.e. reduced fragmentation and thus high ion current for the targeted m/z during analysis. With electron ionisation, the fragmentation that occurs is mainly directed by the introduced group. Enantioseparation with gas chromatography/negative-ion chemical ionisation mass spectrometry of the derivatives was demonstrated for the enantiomers of amphetamine, α-aminocaprylic acid methyl ester and threo-methylphenidate. The new derivatisation reagent shows highly improved mass spectral properties for negative-ion chemical ionisation mass spectrometry and is thus suitable for sensitive chiral detection of amino compounds. The reagent extends the applicability of dissociative resonance electron capture using pentafluorobenzyl derivatives to chiral analysis.

Chiral separation of N‐methyl‐dl‐aspartic acid in rat brain tissue as N‐ethoxycarbonylated (S)‐(+)‐2‐octyl ester derivatives by GC‐MS

A selective and sensitive analytical method was developed for enantiomeric separation and determination of N-methyl-DL-aspartic acid (NMA). The method involved the conversion of each enantiomer into N-ethoxycarbonylated (S)-(+)-2-octyl ester derivative for the direct separation by gas chromatography-mass spectrometry (GC-MS). The diastereomeric derivatives showed characteristic mass spectral properties for analysis by selected ion monitoring mode (SIM) and enabling enantioseparation on an achiral capillary column. Two enantiomers were baseline separated, and the detection limits for N-methyl-L-aspartic acid (NMLA) and N-methyl-D-aspartic acid (NMDA) were 0.07 and 0.03 ng/g, respectively. When applied to rat brain tissues for absolute configuration of NMA, only NMDA was determined, while NMLA was monitored as lower than the limit of detection.