Nitrogen direct analysis in real time time-of-flight mass spectrometry (N2 DART-TOFMS) for rapid screening of forensic drugs.

RATIONALE: Over the last ten years, helium direct analysis in real time time-of-flight mass spectrometry (He DART-TOFMS) has become an established technique in rapid screening of forensic drugs to decrease the time necessary to triage forensic drug cases, therefore contributing to backlog reduction and more timely criminal prosecution. Recently, we demonstrated that N2 DART was able to efficiently ionize all polar compounds except for a few extremely small ones such as methanol and acetonitrile. Therefore, N2 DART-TOFMS should be a suitable technique for rapid screening of forensic drugs. METHODS: Nitrogen direct analysis in real time time-of-flight mass spectrometry (N2 DART-TOFMS) was performed using a JEOL AccuTOF mass spectrometer with an IonSense DART-100 ion source. A 3-min analytical protocol was used for the analysis of each sample. Sample introduction was accomplished by moving the closed end of a melting point capillary where approximately 1 µL sample solution was deposited or the exposed inside of a freshly cut tablet across the N2 gas stream between the DART-100 ion source and orifice 1 of the AccuTOF. RESULTS: Ten commonly abused drugs, eight synthetic cannabinoids and four controlled prescription drugs (CPDs) were analyzed. The limit of detection (LOD) was determined to be approximately 10 µg/mL or 10 pg in quantities. All drugs at the LOD level were positively identified using their [M + H]+ ions with mass errors less than 5 mDa. The identification were further supported by in-source fragment ions and characteristic N2 DART ions that are not commonly generated by He DART, e.g. [M + H + O]+ and [M + H + 2O]+ ions. CONCLUSIONS: It was concluded that the 3-min analytical protocol could be utilized in the analysis of seized drugs in the form of tablets and powders or prepared in solution. In consideration that N2 is readily available in the air and He is a non-renewable resource, N2 DART-TOFMS is a greener, cheaper and more convenient alternative to He DART-TOFMS in rapid screening of forensic drugs.

A photochemical mechanism for homochirogenesis. Part 2.

A theoretical investigation of the photochemistry of racemic compounds with circularly polarized light was undertaken. The exact solutions of the differential equations by numerical integration to the approximate solutions used in an earlier article were compared. The exact solutions showed that sequential reactions yield enhanced optical activities in the products. For irreversible reactions, all enantiomeric excesses are lost if the reactions are carried to completion, but appreciable resolution occurs in many cases for partial conversion. For reversible reactions, significant enantiomeric excesses are found at the photostationary state.

Quantitative real-time monitoring of chemical reactions by autosampling flow injection analysis coupled with atmospheric pressure chemical ionization mass spectrometry.

Although qualitative and/or semiquantitative real-time monitoring of chemical reactions have been reported with a few mass spectrometric approaches, to our knowledge, no quantitative mass spectrometric approach has been reported so far to have a calibration valid up to molar concentrations as required by process control. This is mostly due to the absence of a practical solution that could well address the sample overloading issue. In this study, a novel autosampling flow injection analysis coupled with an atmospheric pressure chemical ionization mass spectrometry (FIA/APCI-MS) system, consisting of a 1 µL automatic internal sample injector, a postinjection splitter with 1:10 splitting ratio, and a detached APCI source connected to the mass spectrometer using a 4.5 in. long, 0.042 in. inner diameter (ID) stainless-steel capillary, was thus introduced. Using this system together with an optional FIA solvent modifier, e.g., 0.05% (v/v) isopropylamine, a linear quantitative calibration up to molar concentration has been achieved with 3.4-7.2% relative standard deviations (RSDs) for 4 replicates. As a result, quantitative real-time monitoring of a model reaction was successfully performed at the 1.63 M level. It is expected that this novel autosampling FIA/APCI-MS system can be used in quantitative real-time monitoring of a wide range of reactions under diverse reaction conditions.

Differentiation of underivatized monosaccharides by atmospheric pressure chemical ionization quadrupole time-of-flight mass spectrometry.

RATIONALE: Differentiation of underivatized monosaccharides is essential in the structural elucidation of oligosaccharides which are closely involved in many life processes. So far, such differentiation has been usually achieved by electrospray ionization mass spectrometry (ESI-MS). As an alternative to ESI-MS, atmospheric pressure chemical ionization mass spectrometry (APCI-MS) should provide complementary results. METHODS: A quadrupole time-of-flight (QTOF) mass spectrometer with accurate mass measurement ability was used with an APCI heated nebulizer ion source because we believe that a recently published article using a single quadrupole mass spectrometer assigned incorrect identities for APCI ions from hexoses. Using APCI-QTOF, the MS(2) and pseudo-MS(3) mass spectra of 11 underivatized monosaccharides were obtained under various collision voltages. The mass spectra were carefully interpreted after accurate mass measurement. RESULTS: Differentiation of three hexoses was achieved by different MS(2) spectra of their [M + NH(4)](+) and [M - H](-) ions. The MS(2) spectra of the [M + NH(4)](+) ions were also used to distinguish methyl α-D-glucose and methyl ß-D-glucose, while the pseudo-MS(3) spectra of the [M + H](+) ions were utilized to differentiate the three hexosamine and N-acetylhexosamine stereoisomers. Unique [M + O(2)](-) ions were observed and their distinctive fragmentation patterns were utilized to differentiate the three hexosamine stereoisomers. CONCLUSIONS: Although ESI coupled with single or triple quadrupole and ion trap mass spectrometers has been widely utilized in the differentiation of monosaccharides, this report demonstrated that APCI-QTOF-MS had its own advantages in achieving the same goal.

Ionization mechanism of positive-ion direct analysis in real time: a transient microenvironment concept.

A transient microenvironment mechanism (TMEM) is proposed to address matrix effects for direct analysis in real time (DART). When the DART gas stream is in contact with the sample, a transient microenvironment (TME), which can shield analytes from direct ionization, may be generated through the desorption of the matrix containing the analyte. The DART gas stream can directly ionize the matrix molecules, but the analytes will be ionized primarily through gas-phase ion/molecule reactions with the matrix ions. Experimental results showed that as little as 10 nL of liquid or 10 microg of solid was able to generate an efficient TME. Generated TMEs were able to control the ionization of an analyte below an analyte-to-matrix ratio that was dependent on the DART temperature and the boiling points of the analyte and matrix. TMEs generated by common solvents were studied in detail. The ionization of both polar and nonpolar compounds, present in a solvent or another analyte below a ratio of 1:100, were found to be mainly controlled by the generated TMEs at a DART temperature of 300 degrees C.

Ionization mechanism of negative ion-direct analysis in real time: a comparative study with negative ion-atmospheric pressure photoionization.

The ionization mechanism of negative ion-direct analysis in real time (NI-DART) has been investigated using over 42 compounds, including fullerenes, perfluorocarbons (PFC), organic explosives, phenols, pentafluorobenzyl (PFB) derivatized phenols, anilines, and carboxylic acids, which were previously studied by negative ion-atmospheric pressure photoionization (NI-APPI). NI-DART generated ionization products similar to NI-APPI, which led to four ionization mechanisms, including electron capture (EC), dissociative EC, proton transfer, and anion attachment. These four ionization mechanisms make both NI-DART and NI-APPI capable of ionizing a wider range of compounds than negative ion-atmospheric pressure chemical ionization (APCI) or negative ion-electrospray ionization (ESI). As the operation of NI-DART is much easier than that of NI-APPI and the gas-phase ion chemistry of NI-DART is more easily manipulated than that of NI-APPI, NI-DART can be therefore used to study in detail the ionization mechanism of LC/NI-APPI-MS, which would be a powerful methodology for the quantification of low-polarity compounds. Herein, one such application has been further demonstrated in the detection and identification of background ions from LC solvents and APPI dopants, including water, acetonitrile, chloroform, methylene chloride, methanol, 2-propanol, hexanes, heptane, cyclohexane, acetone, tetrahydrofuran (THF), 1,4-dioxane, toluene, and anisole. Possible reaction pathways leading to the formation of these background ions were further inferred. One of the conclusions from these experiments is that THF and 1,4-dioxane are inappropriate to be used as solvents and/or dopants for LC/NI-APPI-MS due to their high reactivity with source basic ions, leading to many reactant ions in the background.

Ionization Mechanism of Positive-Ion Nitrogen Direct Analysis in Real Time.

Nitrogen can be an inexpensive alternative to helium used by direct analysis in real time (DART), especially in consideration of the looming helium shortage. Therefore, the ionization mechanism of positive-ion N2 DART has been systematically investigated. Our experiments suggest that a range of metastable nitrogen species with a variety of internal energies existed and all of them were less energetic than metastable helium atoms. However, compounds with ionization energies (IE) equal to or lower than 10.2 eV (all organic compounds except the extremely small ones) can be efficiently ionized. Because N2 DART was unable to efficiently ionize ambient moisture and common organic solvents such as methanol and acetonitrile, the most important ionization mechanism was direct Penning ionization followed by self-protonation of polar compounds generating [M+H]+ ions. On the other hand, N2 DART was able to efficiently ionize ammonia, which was beneficial in the ionization of hydrogen-bonding compounds with proton affinities (PA) weaker than ammonia generating [M+NH4]+ ions and large PAHs generating [M+H]+ ions through proton transfer. N2 DART was also able to efficiently ionize NO, which led to the ionization of nonpolar compounds such as alkanes and small aromatics generating [M-(2m+1)H]+ (m=0,1…) ions. Lastly, metastable nitrogen species was also able to produce oxygen atoms, which resulted in increased oxygen adducts as the polarity of organic compounds decreased. In comparison with He DART, N2 DART was approximately one order of magnitude less sensitive in generating [M+H]+ ions, but could be more sensitive in generating [M+NH4]+ ions. Graphical Abstract ᅟ.

Negative ion-atmospheric pressure photoionization: electron capture, dissociative electron capture, proton transfer, and anion attachment.

To better guide the development of liquid chromatography/electron capture-atmospheric pressure photoionization-mass spectrometry (LC/EC-APPI-MS) in analysis of low polarity compounds, the ionization mechanism of 19 compounds was studied using dopant assisted negative ion-APPI. Four ionization mechanisms, i.e., EC, dissociative EC, proton transfer, and anion attachment, were identified as being responsible for the ionization of the studied compounds. The mechanisms were found to sometimes compete with each other, resulting in multiple ionization products from the same molecule. However, dissociative EC and proton transfer could also combine to generate the same [M - H](-) ions. Experimental evidence suggests that O(2)(-*), which was directly observed in the APPI source, plays a key role in the formation of [M - H](-) ions by way of proton transfer. Introduction of anions more basic than O(2)(-*), i.e., C(6)H(5)CH(2)(-), into the APPI source, via addition of di-tert-butyl peroxide in the solvent and/or dopant, i.e., toluene, enhanced the deprotonation ability of negative ion-APPI. Although the use of halogenated solvents could hinder efficient EC, dissociative EC, and proton transfer of negative ion-APPI due to their EC ability, the subsequently generated halide anions promoted halide attachment to compounds that otherwise could not be efficiently ionized. With the four available ionization mechanisms, it becomes obvious that negative ion-APPI is capable of ionizing a wider range of compounds than negative ion chemical ionization (NICI), negative ion-atmospheric pressure chemical ionization (negative ion-APCI) or negative ion-electrospray ionization (negative ion-ESI).

Liquid chromatography/negative ion atmospheric pressure photoionization mass spectrometry: a highly sensitive method for the analysis of organic explosives.

Gas chromatography/mass spectrometry (GC/MS) is applied to the analysis of volatile and thermally stable compounds, while liquid chromatography/atmospheric pressure chemical ionization mass spectrometry (LC/APCI-MS) and liquid chromatography/electrospray ionization mass spectrometry (LC/ESI-MS) are preferred for the analysis of compounds with solution acid-base chemistry. Because organic explosives are compounds with low polarity and some of them are thermally labile, they have not been very well analyzed by GC/MS, LC/APCI-MS and LC/ESI-MS. Herein, we demonstrate liquid chromatography/negative ion atmospheric pressure photoionization mass spectrometry (LC/NI-APPI-MS) as a novel and highly sensitive method for their analysis. Using LC/NI-APPI-MS, limits of quantification (LOQs) of nitroaromatics and nitramines down to the middle pg range have been achieved in full MS scan mode, which are approximately one order to two orders magnitude lower than those previously reported using GC/MS or LC/APCI-MS. The calibration dynamic ranges achieved by LC/NI-APPI-MS are also wider than those using GC/MS and LC/APCI-MS. The reproducibility of LC/NI-APPI-MS is also very reliable, with the intraday and interday variabilities by coefficient of variation (CV) of 0.2-3.4% and 0.6-1.9% for 2,4,6-trinitrotoluene (2,4,6-TNT).