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Saliva is a body fluid that is much easier to collect and analyze than blood. Thus, saliva analysis for the detection of delta 9‐tetrahydrocannabinol (delta 9‐THC) can serve as a tool for law enforcement agents to detect cannabis consumption by drivers. Fast saliva analysis for the presence of delta 9‐THC and/or cannabidiol (CBD) is described with both gas chromatography–mass spectrometry (GC–MS) with Cold electron ionization (EI) with good separation and in 10 min and/or with Open Probe Fast GC–MS with Cold EI in under 1 min full analysis cycle time. Saliva was taken directly from donors' tongues on a thin glass rod that was used "as is" for analysis. The saliva was thermally desorbed with a modified ChromatoProbe device inside the gas chromatograph (GC) injector and in an Open Probe (Agilent name QuickProbe) for its sub‐1‐min analysis. Cold EI is based on coupling of the GC and mass spectrometer (MS) with a supersonic molecular beam and on EI of vibrationally cold sample molecules during their flight through a contact‐free ion source (thereby named Cold EI). A revised type of Open Probe Fast GC–MS on the bench is also described. Our saliva analysis was characterized by: Saliva can be collected in the field and transported to the lab for analyses "as is" without any sample preparation.Easy detection of cannabis consumption from cigarettes and/or other cannabis products.Distinction between the isomers delta 9‐THC and CBD.Ultra‐fast analysis in under 1 min using Open Probe Fast GC–MS with Cold EI. [ABSTRACT FROM AUTHOR]

Gas chromatography–mass spectrometry (GC–MS) with Cold EI is based on interfacing GC and MS with supersonic molecular beams (SMBs) along with electron ionization of vibrationally cold sample compounds in SMB in a fly‐through ion source (hence the name Cold EI). Cold EI improves all the central performance aspects of GC–MS, and in this paper, we focus on its improvement of signal‐to‐noise ratio (S/N) and limits of detection (LODs). We found that the harder the compound for analysis with standard EI, the greater the Cold EI gain in S/N and LOD. The lower LOD and higher S/N of Cold EI emerge from a few reasons: (a) similar ionization yield as standard EI, (b) enhanced abundance of molecular ions, (c) elimination of vacuum background noise, (d) elimination of ion source‐related peak tailing and degradation, (e) ability to lower the elution temperatures via the use of high column flow rates, and (f) greater range of thermally labile and low‐volatility compounds that can be analyzed. We demonstrate the superior S/N and lower LOD of Cold EI versus standard EI in a range of compounds, from the simple‐to‐analyze octafluoronaphthalene all the way to reserpine and an organo‐metallic compound that cannot be analyzed by standard EI. These compounds include methyl stearate, cholesterol, n‐C32H66, large polycyclic aromatic hydrocarbons, dioctyl phthalates, diundecyl phthalate, pentachlorophenol, benzidine, lambda‐cyhalothrin, and methidathion. The significantly lower Cold EI LODs that can be over 1000 times better than in standard EI further result in far superior response linearity and greater measurement dynamic range. [ABSTRACT FROM AUTHOR]

Gas chromatography–mass spectrometry (GC‐MS) with Cold EI is based on interfacing GC and MS with a supersonic molecular beam (SMB) and sample compounds ionization with a fly‐through ion source as vibrationally cold compounds in the SMB (hence the name Cold EI). We explored the use of nitrogen and hydrogen as carrier and make‐up gases with Cold EI and found:Nitrogen is very effective in cooling compounds in SMB and while helium requires 60 ml/min nitrogen provides effective cooling with only 7–8 ml/min combined column and make‐up flow rate. Hydrogen is less effective than helium and requires higher flow rates.The transition from helium to nitrogen (or hydrogen) is simple and fast and requires just closing the helium valve and opening the nitrogen valve.The same column used with helium can be used with nitrogen or hydrogen.The same elution times could be obtained with nitrogen or hydrogen as with helium.The GC separation with nitrogen was reduced compared with helium and peak widths were increased by an average factor of 1.5 for similar elution times. Hydrogen provided ~0.7 narrower peak widths than helium.The signal with nitrogen was reduced compared with helium by an average factor of 3.3 and the signal loss was reduced with higher compounds mass. With hydrogen the signal loss was about a factor of 1.5 but the baseline noise was higher thus with similar S/N as with nitrogen.USEPA 8270 semivolatile mixture was easily analyzed with both nitrogen and hydrogen carrier gases. [ABSTRACT FROM AUTHOR]

Cannabis extracts and products were analyzed by gas chromatography–mass spectrometry (GC–MS) with Cold EI for their full content including terpenes, sesquiterpenes, sesquiterpinols, fatty acids, delta 9‐tetrahydrocannabinol (THC), cannabidiol (CBD), other cannabinoids, hydrocarbons, sterols, diglycerides, triglycerides, and impurities. GC–MS with Cold EI is based on interfacing GC and MS with supersonic molecular beams (SMB) along with electron ionization of vibrationally cold sample compounds in the SMB in a fly‐through ion source (hence the name Cold EI). GC–MS with Cold EI improves all the performance aspects of GC–MS, enables the analysis of Cannabinoids with OH groups without derivatization, while providing enhanced molecular ions for improved identification, and enables internal quantitation without calibration. We found over 50 cannabinoid compounds including a new one with a Cold EI mass spectrum very similar to delta 9‐THC as well as relatively large cannabinoids with molecular weight above m/z = 400. Because the analysis was universal in full scan and not targeted, we found impurities such as bromo CBD and fluticasone propionate and could monitor the formation of oxidized CBD during decarboxylation. In addition, GC–MS with Cold EI enabled nontargeted full analysis of terpenes, sesquiterpenes, and sesquiterpinols in cannabis extracts with good internal quantitation. GC–MS with Cold EI further served with very good sensitivity for the concentration determination of delta 9‐THC in CBD‐related products. Finally, cannabis drugs such as EP‐1 used in Israel for treatment of epilepsy and for children with autism spectrum disorder (ASD) were analyzed for their full cannabinoids content for learning on the entourage effect and for drug activity optimization. [ABSTRACT FROM AUTHOR]

Pharmaceuticals require careful and precise determination of their impurities that might harm the user upon consumption. Although today, the most common technique for impurities identification is liquid chromatography-mass spectrometry (LC-MS/MS), it has several downsides due to the nature of the ionization method. Also, the analyses in many cases are targeted thus despite being present, some of the compounds will not be revealed. In this paper, we propose and show a new method for untargeted analysis and identification of impurities in active pharmaceutical ingredients (APIs). The instrument used for these analyses is a novel electron ionization (EI) LC-MS with supersonic molecular beams (SMB). The EI-LC-MS-SMB was implemented for analyses of several drug samples spiked with an impurity. The instrument provides EI mass spectra with enhanced molecular ions, named Cold EI, which increases the identification probabilities when the compound is identified with the aid of an EI library like National Institute of Standards and Technology (NIST). We analyzed ibuprofen and its impurities, and both the API and the expected impurity were identified with names and structures by the NIST library. Moreover, other unexpected impurities were found and identified proving the ability of the EI-LC-MS-SMB system for truly untargeted analysis. The results show a broad dynamic range of four orders of magnitude at the same run with a signal-to-noise ratio of over 10 000 for the API and almost uniform response. [ABSTRACT FROM AUTHOR]

A new type of photoionization ion source was developed for the ionization of cold molecules in supersonic molecular beams (named Cold PI). The system was based on a GC–MS with supersonic molecular beams and its fly-through EI of cold molecules ion source (Cold EI) plus quadrupole mass analyzer. A continuously operated deuterium VUV photoionization lamp was added and placed above and between the supersonic nozzle and skimmer whereas the Cold EI ion source served only as a portion of the ion transfer ion optics. The supersonic nozzle and skimmer were voltage biased and the VUV light crossed the supersonic expansion about 10 mm from the nozzle. We obtained over three orders of magnitude enhancement in the relative abundance of the molecular ion of squalane in Cold PI versus in photoionization of this compound as a thermal compound. Accordingly, we also proved that standard photoionization is not as soft ionization method as previously perceived for large compounds. We found that Cold PI is as soft as and possibly softer than field ionization; thus, it could be the softest known ionization method. The ionization yield was about 200–300 times weaker than with Cold EI yet our limit of detection was about 200 femtogram in SIM mode for cholesterol and pyrene which is reasonable. Practically, all hydrocarbons gave only molecular ions with rather uniform response whereas alcohols gave some molecular ions plus major fragment ions particularly with a loss of water (similarly to field ionization). We tested Cold PI in the GC–MS analysis of diesel fuels and analyzed the time averaged data for group type information. We also found that we can analyze the diesel fuels by fast under 20-s flow injection analysis in which the generated averaged mass spectrum of molecular ions only could serve for the characterization of fuels. [ABSTRACT FROM AUTHOR]

The heavy petroleum fractions produced during refining processes need to be upgraded to useable products to increase their value. Hydrogenated heavy paraffinic fractions can be oxidised to produce high value products that contain a variety of oxygenates. These heavy oxygenated paraffinic fractions need to be characterised to enable the control of oxidation processes and to understand product properties. The accurate identification of the oxygenates present in these fractions by electron ionisation (EI) mass spectrometry is challenging due to the complexity of these heavy fractions. Adding to this challenge is the limited applicability of EI mass spectral libraries due to the absence of molecular ions from the EI mass spectra of many oxygenates. The separation of oxygenates from the complex hydrocarbon matrix prior to high temperature GC-MS (HT-GC-MS) analysis reduces the complexity of these fractions and assists in the accurate identification of these oxygenates. Solid phase extraction (SPE) and supercritical fluid chromatography (SFC) were employed as prefractionation techniques. GC-MS with supersonic molecular beams (SMBs) (also named GC-MS with cold-EI) utilises a SMB interface with which EI is done with vibrationally cold sample compounds in a fly-through ion source (cold-EI) resulting in a substantial increase in the molecular ion signal intensity in the mass spectrum. This greatly enhances the accurate identification of the oxygenates in these fractions. This study investigated the ionisation behaviour of oxygenated compounds using cold-EI. The prefractionation by SPE and SFC and the subsequent analysis with GCMS with cold-EI were applied to an oxygenated heavy paraffinic fraction. [ABSTRACT FROM AUTHOR]

Rationale Library-based compound identification with electron ionization (EI) mass spectrometry (MS) is a well-established identification method which provides the names and structures of sample compounds up to the isomer level. The library (such as NIST) search algorithm compares different EI mass spectra in the library's database with the measured EI mass spectrum, assigning each of them a similarity score called 'Match' and an overall identification probability. Cold EI, electron ionization of vibrationally cold molecules in supersonic molecular beams, provides mass spectra with all the standard EI fragment ions combined with enhanced Molecular Ions and high-mass fragments. As a result, Cold EI mass spectra differ from those provided by standard EI and tend to yield lower matching scores. However, in most cases, library identification actually improves with Cold EI, as library identification probabilities for the correct library mass spectra increase, despite the lower matching factors. Methods This research examined the way that enhanced molecular ion abundances affect library identification probability and the way that Cold EI mass spectra, which include enhanced molecular ions and high-mass fragment ions, typically improve library identification results. It involved several computer simulations, which incrementally modified the relative abundances of the various ions and analyzed the resulting mass spectra. Results The simulation results support previous measurements, showing that while enhanced molecular ion and high-mass fragment ions lower the matching factor of the correct library compound, the matching factors of the incorrect library candidates are lowered even more, resulting in a rise in the identification probability for the correct compound. Conclusions This behavior which was previously observed by analyzing Cold EI mass spectra can be explained by the fact that high-mass ions, and especially the molecular ion, characterize a compound more than low-mass ions and therefore carries more weight in library search identification algorithms. These ions are uniquely abundant in Cold EI, which therefore enables enhanced compound characterization along with improved NIST library based identification. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

A new type of electron ionization LC-MS with supersonic molecular beams (EI-LC-MS with SMB) is described. This system and its operational methods are based on pneumatic spray formation of the LC liquid flow in a heated spray vaporization chamber, full sample thermal vaporization and subsequent electron ionization of vibrationally cold molecules in supersonic molecular beams. The vaporized sample compounds are transferred into a supersonic nozzle via a flow restrictor capillary. Consequently, while the pneumatic spray is formed and vaporized at above atmospheric pressure the supersonic nozzle backing pressure is about 0.15 Bar for the formation of supersonicmolecular beams with vibrationally cold sample molecules without cluster formation with the solvent vapor. The sample compounds are ionized in a fly-though EI ion source as vibrationally cold molecules in the SMB, resulting in 'Cold EI' (EI of vibrationally cold molecules) mass spectra that exhibit the standard EI fragments combined with enhanced molecular ions. We evaluated the EI-LC-MS with SMB systemand demonstrated its effectiveness in NIST library sample identification which is complemented with the availability of enhanced molecular ions. The EI-LC-MS with SMB system is characterized by linear response of five orders of magnitude and uniformcompound independent response including for non-polar compounds. This feature improves sample quantitation that can be approximated without compound specific calibration. Cold EI, like EI, is free from ion suppression and/or enhancement effects (that plague ESI and/or APCI) which facilitate faster LC separation because full separation is not essential. The absence of ion suppression effects enables the exploration of fast flow injection MS-MS as an alternative to lengthy LC-MS analysis. These features are demonstrated in a few examples, and the analysis of the main ingredients of Cannabis on a few Cannabis flower extracts is demonstrated. Finally, the advantages of EI-LC-MS with SMB are listed and discussed. [ABSTRACT FROM AUTHOR]

Abstract: A new type of gas chromatograph mass spectrometer (GC–MS) was used for semi-online monitoring of organic chemical reactions for their yield optimization, mechanism elucidation, and for obtaining information on the reaction products identity and purity. It was used with reaction mixtures without prior separation and purification as needed for NMR, thereby saving time and effort. Our unique GC–MS named 5975-SMB Supersonic GC–MS is based on GC interface with the MS with supersonic molecular beams (SMB) and on ionization of the sample molecules during their axial flight through an open electron ionization ion source as vibrationally cold molecules. GC–MS with SMB is demonstrated to significantly extend the range of compounds amenable for analysis, practically always giving molecular ions, enabling effective fast GC–MS analysis, and providing elemental formulas via isotope abundance analysis with unit mass resolution quadrupole MS. In addition, it uniquely provides uniform response to all compounds, a feature, which is vital for the measurement of chemical reaction yields. In this manuscript, four different organic synthetic reactions were studied and are described. Based on the collected data, we were able to better understand how the reaction conditions should be optimized in order to maximize the yields and purity of target products. Consequently, we propose that GC–MS with SMB can serve as a novel tool for the fast optimization of chemical reactions. [Copyright &y& Elsevier]

An improved electron ionization (EI) ion source is described, based on the modification of a Brink-type EI ion source through the addition of a second cage with a fine mesh outside the ion chamber. The added outer cage shields the inner ion cage (ionization zone) against the penetration of the filament and electron repeller potentials, and thus results in the provision of ions with narrower ion energy distribution, hence improved ion-beam quality. The closer to zero electrical field inside the ion cage enables improved filtration (rejection) of ions that are produced from vacuum background compounds, based on difference in ion energies of beam and background species. The improved background ion filtration and ion-beam quality resulted in 2.6 times higher mass spectrometric ion signal, combined with 6.4 times better signal to noise ratio, in comparison with the same ion source having a single cage. The dual cage ion source further provides a smaller or no reduction of the electron emission current upon lowering the electron energy for achieving softer EI and/or electron attachment ionization. It also improves the long-term mass spectral and signal reproducibility and enables fast, automated change of the electron energy. Consequently, the dual cage EI ion source is especially effective for use with gas chromatography mass spectrometry with supersonic molecular beams (SMB), liquid chromatography mass spectrometry with SMB, ion guns with SMB, and any other experimental systems with SMB or nonthermal molecular beams. [ABSTRACT FROM AUTHOR]

Abstract: A new type of low thermal mass (LTM) fast gas chromatograph (GC) was designed and operated in combination with gas chromatography mass spectrometry (GC–MS) with supersonic molecular beams (SMB), including GC–MS–MS with SMB, thereby providing a novel combination with unique capabilities. The LTM fast GC is based on a short capillary column inserted inside a stainless steel tube that is resistively heated. It is located and mounted outside the standard GC oven on its available top detector port, while the capillary column is connected as usual to the standard GC injector and supersonic molecular beam interface transfer line. This new type of fast GC–MS with SMB enables less than 1min full range temperature programming and cooling down analysis cycle time. The operation of the fast GC–MS with SMB was explored and 1min full analysis cycle time of a mixture of 16 hydrocarbons in the C10H22 up to C44H90 range was achieved. The use of 35mL/min high column flow rate enabled the elution of C44H90 in less than 45s while the SMB interface enabled splitless acceptance of this high flow rate and the provision of dominant molecular ions. A novel compound 9-benzylazidanthracene was analyzed for its purity and a synthetic chemistry process was monitored for the optimization of the chemical reaction yield. Biodiesel was analyzed in jet fuel (by both GC–MS and GC–MS–MS) in under 1min as 5ppm fatty acid methyl esters. Authentic iprodion and cypermethrin pesticides were analyzed in grapes extract in both full scan mode and fast GC–MS–MS mode in under 1min cycle time and explosive mixture including TATP, TNT and RDX was analyzed in under 1min combined with exhibiting dominant molecular ion for TATP. Fast GC–MS with SMB is based on trading GC separation for speed of analysis while enhancing the separation power of the MS via the enhancement of the molecular ion in the electron ionization of cold molecules in the SMB. This paper further discusses several features of fast GC and fast GC–MS and the various trade-offs involved in having powerful and practical fast GC–MS. [Copyright &y& Elsevier]

Open Probe is based on a vaporization oven mounted on a transfer line of a gas chromatograph mass spedrometer (GC/MS) which is connected to the MS ion source via a short flow resthction capillary. The probe oven is open to room air while having helium purge flow protection to eliminate or significantly reduce air leakage into the oven and MS ion source. Sample analysis can be as simple as touch (the sample), push (the sample holder) into the open probe oven, and have the results. Experiments were performed with a GC/MS with supersonic molecular beams and with a standard Agilent 5975 MSD. Powders and tablets analysis were performed by touching the sample with the bottom side of a melting point vial and inserting it into the open probe oven with total analysis cycle lime of <30 s. Similarly, trace trinitrotoluene (TNT) on human fingerprints was analyzed. Additional sample holder types included swabs, spoons, and vials. The open probe is a leak-proof MS probe which is characterized by fast analysis cycle time, and it uses a low cost mass spectrometer of GC/MS with the benefits of electron ionization of library search and uniform, quantitative response without ion suppression effects. [ABSTRACT FROM AUTHOR]

Abstract: Malaria is one of the most widespread and deadly diseases on the planet. Every year, about 500 million new cases are diagnosed, and the annual death toll is about 3 million. Primaquine has strong antiparasitic effects against gametocytes and can therefore prevent the spread of the parasite from treated patients to mosquitoes. It is also used in radical cures and prevents relapse. Consequently, primaquine is an often-used drug. In this study the separation of unprocessed primaquine from the contaminant quinocide based on gas chromatography–mass spectrometry with supersonic molecular beam (SMB) is presented and 7.5mg primaquine diphosphate tablets were analyzed. We present a novel method for fast determination of quinocide which is an isomer of primaquine as the main contaminant in unprocessed primaquine and in its medical form as tablets by gas chromatography–mass spectrometry with SMB (also named supersonic GC–MS). Supersonic GC–MS provides enhanced molecular ion without any ion source related peak tailing plus extended range of compounds amenable for GC–MS analysis. In addition, major isomer mass spectral effects were revealed in the mass spectra of primaquine and quinocide which facilitated the unambiguous identification of quinocide in primaquine tablets. Fast GC–MS analysis is demonstrated with less then 2min elution time of the drug and its main contaminants. [Copyright &y& Elsevier]

Electrospray LC–MS, LC–MS with Cold EI and GC–MS with Cold EI (Electron Ionization (EI) of vibrationally cold molecules in supersonic molecular beams (SMB)) are compared in their sample identification capabilities. Two test mixtures were used: (a) acetaminophen, caffeine, sulfadimethoxine, terfenadine and reserpine; and (b) octafluoronaphthalene (OFN), pyrene, cholesterol and agidol 40. The major strength of EI in both LC–MS with Cold EI and GC–MS with Cold EI is its compatibility with library based sample identification that provides samples names and structures at the isomer level. GC–MS with Cold EI alleviates two major downsides of GC–MS with standard EI as it provides enhanced molecular ions that are often weak or missing in standard EI and, it significantly extends the range of compounds that are amenable for analysis. Consequently, reserpine and agidol 40 that are incompatible with standard GC–MS analyses are analyzed by GC–MS with Cold EI and yield effective library based identification. In cases involving sample compounds that are not in the library, ESI–LC–MS provides elemental formula information (when combined with high resolution MS) while GC–MS with Cold EI also provides elemental formula when TAMI software is used for the quadrupole mass accuracy improvement combined with isotope abundance analysis. We found that both LC–MS with Cold EI and GC–MS with Cold EI have broader range of small molecules amenable for analysis than ESI–LC–MS that fails to analyze relatively non-polar compounds and exhibits highly non-uniform and compound dependent ionization yields that span over four orders of magnitude. The total ion mass chromatograms S/N of ESI–LC–MS and LC–MS with Cold EI are comparable while it is better (>100 times per on-column amount) for GC–MS with Cold EI. [ABSTRACT FROM AUTHOR]