Complementary use of gas chromatography-mass spectrometry, gas chromatography-atomic emission detection and nuclear magnetic resonance for identification of pharmaceutically related impurities of unknown structures

The complementary use of gas chromatography-mass spectrometry (GC-MS), gas chromatography-atomic emission detection (GC-AED) and nuclear magnetic resonance (NMR) spectroscopy is demonstrated by the identification of four major by-products in a sample from an exploratory attempt to synthesise 1.3-dichloro-5-(difluoromethoxy)benzene. GC-MS was used for straightforward identification of the target compound and one of the impurities. By employing GC-AED, the sample was screened for heteroatoms in the analysed molecules and determination of the partial empirical formula of one sample component was carried out. The combined spectroscopic data obtained from the MS and AED experiments facilitated structure elucidation of two of the additional by-products. Finally, identification of the last unknown component could be obtained by combining spectral information from GC-MS, GC-AED and NMR data acquired after isolation of the impurity from the sample.     

Identification of chlorinated sulfur compounds in pulp mill effluents by GC-MS and GC-AED

Summary Three chlorinated dimethyl sulfones and five chlorinated thiophenes have been identified in the alkaline extraction liquor from a bleach plant by gas chromatography with atomic emission detection (GC-AED) and with mass spectrometry (GC-MS). The information on elemental content obtained by GC-AED enabled a rapid screening of the sulfur compounds and provided important structural information complementary to the mass spectral data. Quantitation was accomplished by GC-AED based on universal calibration.     

Determination of brominated alkylbenzenes in nickel industry sludge by capillary gas chromatography

Summary Capillary gas chromatography coupled to both mass spectrometry (GCMS) and atomic emission spectroscopy (GC-AED) was studied for the analysis of bromine-containing alkylbenzenes present in sludge from a nickel refinery. Owing to the high abundance of chlorinated compounds, location of the brominated species was difficult based on GC-MS with electron ionization. In contrast, GC-MS with negative chemical ionization (GC-NCIMS) and GC-AED enabled bromine-selective detection and were utilized for an effective location of the brominated compounds. Bromine-selective detection by GC-NCIMS relied on the monitoring of Br⁻ (m/z 79/81) with CH₄ as ionization gas, while atomic emission (827.2 nm) from a helium plasma was utilized in the case of GC-AED. While GC-NCIMS was 30–500 times more sensitive than GC-AED, the latter technique was superior for quantitative purposes. Because the bromine response of the AED was independent of molecular structure, quantification was possible without reference material.     

Phenyl-substituted polycyclic aromatic compounds as intermediate products during pyrolytic reactions involving coal tars, pitches and related materials

Summary Several so far unreported phenyl-substituted polycyclic, aromatic compounds were detected in coal tars, coal tar pitches and ring furnace flue gases by their gas chromatographic retention and mass spectra. In the case of thiophene-derived compounds, the elemental sulfur traces obtained by GC-AED supplied further evidence of their identity. Pure authentic substances were synthesised and analysed by GC-MS and GC-AED to prove the identity of the unknown compounds. Concentration profiles of phenyldibenzofurans and phenyldibenzothiophenes in different coal tars, coal tar pitches and ring furnace flue gases are reported. Reaction mechanisms are proposed which suggest that during oxidative pyrolysis phenyldibenzofurans and phenyldibenthiophene are the intermediate products on the path from dibenzofuran and dibenzothiophene to triphenyleno[1,12-bcd]furan and benzobisbenzofurans, and the respective thiophenes.     

Two-dimensional searching of unknowns using GC retention index data and vapor phase IR data

The use of capillary GC retention data as a second independent search dimension in the GC-FT-IR analyses of unknown samples is examined. A reference retention index library is used along with a reference vapor phase infrared library in order to improve and assist in the identification of unknown compounds.     

Application of gas chromatography-cryocondensation-Fourier transform infrared spectroscopy and gas chromatography-mass spectrometry to the identification of gas phase reaction products from the alpha-pinene/ozone reaction

The gas phase reaction of alpha-pinene with the atmospheric oxidant ozone was investigated by using the capabilities of both gas chromatography-cryocondensation-Fourier transform infrared spectroscopy (GC-FT-IR) and gas chromatography-mass spectrometry (GC-MS), for the identification of the reaction products formed. The reaction was carried out in a flow reaction chamber from where the compounds were sampled on Tenax-containing adsorption cartridges. The reaction mixture was injected onto the column after thermodesorption and analyzed using both GC-IR and GC-MS. Twenty compounds could be detected, including the reactant alpha-pinene and it's impurities tricyclene and camphene. Eleven compounds were identified by spectra comparison with either reference data or spectra obtained from commercial standards. Four compounds were tentatively identified from their IR and MS spectra, while from the remaining two compounds the nature of basic functional groups could be established.     

Detection and identification of loline and its analogues in horse urine

Several kinds of loline-type alkaloids, norloline, loline, N-acetylnorloline, N-acetylloline, N-formylnorloline, N-formylloline and N-methylloline were detected in the urine of race-horses. Furthermore, a new compound of the alkaloids, N-senecioylnorloline, was also found and identified. These compounds were mainly identified by means of gas chromatography-mass spectrometry (GC-MS) and gas chromatography-fourier transform-infrared spectrometry (GC-FT-IR). A certain plant of Gramineae containing four kinds of loline-type alkaloids was found in a bale of hay used for the horse forage. The taxonomic feature of the plant was different from known plants containing loline-type alkaloids. The common fragmentation of loline-type alkaloids under electron ionization was briefly discussed.     

燃油燃料含硫化合物形态分布剖析技术研究进展

介绍了目前用于燃油、燃料(如汽油、柴油、煤油、喷气燃料)的硫化物形态分布剖析的多种分析技术,包括电化学方法和气相色谱与多种选择性检测器联用的方法(如GC - FPD、GC - AED、GC - SCD、GC - MS等),并对各种分析技术的研究现状进行了概述.     

Review of the analytical techniques for sesquiterpenes and sesquiterpene lactones

In this paper the analytical techniques of about the last 2 decades for sesquiterpenes including their lactones are reviewed. For sesquiterpenes, methods like GC, GC-EI-MS, GC-CI-MS, GC-MS-MS, GC-FT-IR, GC-UV, GC-AES, 13C-NMR, PY-GC-MS, HPLC, HPLC-TSP, SFE, SFC, SFC-UV are available, GC combined with MS is the most widespread. Sesquiterpene lactones can be analysed by HPLC, HPLC-TSP, HPLC-APCI, HPLC-ESI, HPLC-PB, HPLC-NMR, SFC, MEKC, GC, GC-MS, TLC and OPLC. Here HPLC is the method of choice. The usefulness of the individual methods are briefly discussed.     

Mass spectrometric and gas and high-performance liquid chromatographic behaviour of an impurity in 2,5-hexanedione

The analysis of 2,5-hexanedione, a metabolic compound of several industrial solvents, is normally carried out using gas chromatographic (GC) or GC-mass spectrometric (MS) techniques. This work, with the aim of verifying the possibility of determining the diketone by means of a high-performance liquid chromatographic (HPLC) method with UV detection, illustrates the importance of the choice of a 2,5-hexanedione standard for the determination of the diketone response factor. In some commercial diketone samples the presence of an impurity, which may interfere with the analysis of the target analyte, was ascertained. This impurity showed GC and HPLC behaviour similar to that of 2,5-hexanedione, but gave a very different UV response. This impurity was identified as 3-methylcyclopent-2-enone by means of MS, GC-MS, HPLC-photodiode-array detection, IR and UV spectrometry. The structure was confirmed by comparing the chromatographic, mass and ultraviolet data of the unknown compound with those of a synthesized reference sample. The well known difficulty in determining 2,5-hexanedione by HPLC with UV detection was reconfirmed owing to its low molar absorptivity.     

Gas chromatography with spectroscopic detectors.

In recent years, capillary gas chromatography (GC) with Fourier Transform Infrared (FT-IR) and/or mass spectral (MS) detection has become a primary analytical tool for qualitative and quantitative analysis of complex mixtures. Because of the wide range of applications, the analytical requirements have motivated a variety of chromatographic and detection developments. This review examines those, illustrating with applications that demonstrate the power of GC and multidimensional GC-MS, GC-FT-IR and GC-FT-IR-MS systems for solving a variety of analytical problems. In addition, the article discusses the integrated performance of such analytical systems with the aid of recent sample introduction and computer data analysis advances.     

非法冰毒晶体中有机杂质的气相色谱-质谱分析

建立了一种适用于分析冰毒杂质的方法,并分析其形成原因。将冰毒样品溶于1 mL 0.1 mol/L pH7.0的磷酸盐缓冲液(4份缓冲液1份10%Na2CO3),杂质用0.5 mL乙酸乙酯萃取。结果共有8种物质被检出。N-甲酰甲基安非他明、N-乙酰甲基安非他明在样品中出现,说明此批冰毒由苯丙酮(phenyl-2-propanone,P-2-P)经Leuckart法合成。N-乙基甲基安非他明的检出,则说明用于合成此批冰毒的P-2-P由苯甲醛和硝基乙烷合成。从实验结果看,该法可以满足冰毒杂质分析的需要,为分析冰毒杂质成分的成因、判断冰毒样品的合成路径提供重要信息。     

Compound-Independent Calibration by Gas Chromatography-Atomic Emission Detection (GC-AED): Analysis of Molecules with 12 Carbon Atoms

ABSTRACT

This study was designed to demonstrate that Gas Chromatography–Atomic Emission Detection (GC-AED) can be used to set in a Compound-independent calibration (CIC) for quantifying organic compounds with various chemical functions using one reference compound. Experiments were carried out with thirteen organic molecules containing twelve atoms of carbon and different amount of hydrogen, oxygen or sulphur.

The results obtained show that the GC-AED technique allows to quantify a molecule of known chemical structure using the elemental response of C or H and another different molecule as the standard of calibration.     

Enhanced monitoring of biopharmaceutical product purity using liquid chromatography-mass spectrometry

LC-MS is a widely used technique for impurity detection and identification. It is very informative and generates huge amounts of data. However, the relevant chemical information may not be directly accessible from the raw data map, particularly in reference to applications where unknown impurities are to be detected. This study demonstrates that multivariate statistical process control (MSPC) based on principal component analysis (PCA) in conjunction with multiple testing is very powerful for comprehensive monitoring and detection of an unknown and co-eluting impurity measured with liquid chromatography-mass spectrometry (LC-MS). It is demonstrated how a spiked impurity present at low concentrations (0.05% (w/w)) is detected and further how the contribution plot provides clear diagnostics of the unknown impurity. This tool makes a fully automatic monitoring of LC-MS data possible, where only relevant areas in the LC-MS data are highlighted for further interpretation.     

Rapid determination of total sulfur in fuels using gas chromatography with atomic emission detection

The purpose of this study is to determine whether gas chromatography (GC)-atomic emission detection (AED) can be used in a low-resolution mode for rapid, accurate determinations of total sulfur in fuels at trace levels to complement other popular methods of total sulfur analysis. A method for the rapid determination of total sulfur in fuels (called "fast GC-AED") is developed. The method is tested on gasoline, jet fuel, kerosene, and diesel fuel with sulfur concentrations ranging from 125 mg/L down to 2.5 mg/L. Fast GC-AED shows better performance than traditional GC-AED for total sulfur determinations, especially for complex mixtures containing many different sulfur-containing compounds at trace levels. This method also shows that GC-AED can be used for both rapid determinations of total sulfur and traditional determinations of speciated sulfur without requiring equipment changes. Fast GC-AED is competitive with other popular methods for sulfur analysis. The 5-min program that is developed for fast GC-AED is comparable with the time scale of other methods, such as wavelength dispersive X-ray fluorescence and UV-fluorescence (2 to 5 min). Fast GC-AED also compares favorably with UV-fluorescence for trace sulfur determinations, demonstrating accuracy down to 2.5-mg/L sulfur.     

Multiresidue screening of pesticides in foods using retention time locking, GC-AED, database search, and GC/MS identification

Fruit and vegetable extracts were screened for over 400 pesticides by gas chromatography with atomic emission detection (GC-AED) and an experimental database. A technique called retention time locking was used to match GC-AED and GC with mass spectrometry (MS) retention times to those of the database. Samples were analyzed for sulfur, nitrogen, phosphorus, and chlorine by GC-AED. Possible pesticides were suggested by database search and identified by GC/MS. Forty-four pesticide standards were analyzed to determine the precision of retention time matching and the accuracy of the database search. Analytical retention times matched database retention times within 0.32 min. Using elemental criteria, the database search identified the correct compound for 41 of 44 pesticide standards. For blind spikes of fruit and vegetable extracts, the database suggested 22 of 26 spiked pesticides as matches. Nineteen were identified by GC/MS. The combination of retention time locking, GC-AED, database search, and GC/MS can be a powerful tool for identifying pesticides in a complex matrix.     

气相色谱法测定催化柴油中硫化物类型分布及数据对比

采用气相色谱-氢火焰离子化检测器-硫化学发光检测器（GC—FID—SCD）联用技术,建立了催化柴油中各种硫化物类型分布的分析方法。考察了色谱条件对催化柴油中各种硫化物分离的影响,定性了某催化柴油中的120多个硫化物,该方法还可以同时提供催化柴油中正构烷烃含量的分布信息。硫化物中的硫在1．5—700mg／L时其峰面积与质量浓度呈较好的线性关系,相关系数达0．9999,响应与硫化物的类型无关。催化柴油中苯并噻吩、4-甲基苯并噻吩、二苯并噻吩、4-甲基二苯并噻吩和4,6-二甲基二苯并噻吩等主要硫化物浓度测定的相对标准偏差（RSD）均小于5．0％。当信噪比（S／N）为3时,测得苯并噻吩硫的检出限为0．1mg／L。将该方法用于不同来源柴油中各种硫化物类型分布的研究,并与气相色谱一原子发射光谱检测器（GC—AED）测硫的数据进行了对比,两种检测器的定量结果大多数具有较好的相关性,相关系数大于0．95。     

Monitoring and Statistical Analysis of Formation of Organochlorine and Organobromine Compounds in Drinking Water of Different Water Intakes

The main drawback of drinking water chlorination involves the formation of quite hazardous disinfection by-products (DBPs), represented mainly by halogenated species. Based on the authors’ monitoring data since 2002, the prevalence of chlorine over bromine in the composition of volatile DBPs was shown for the drinking water in Ufa (Russia). However, the situation was completely reversed in the case of semi-volatile DBPs. The principal goal of the present study involved rationalization of the results of the long-term monitoring. Gas chromatography–mass spectrometry (GC-MS) was used for the qualitative and quantitative analysis of volatile DBPs. Identification of semi-volatile compounds was carried out with GC-MS, while gas chromatography with an atomic emission detector (GC-AED) was used for their quantification. A significant contribution of oxygen to the composition of semi-volatile compounds proves the decisive role of the dissolved organic matter oxidative destructive processes. Statistical analysis revealed notable linear correlations for trihalomethane and haloacetic acid formation vs. chlorine dose. On the contrary, halogenated semi-volatile products do not demonstrate any correlations with the water quality parameters or chlorine dose. Principal component analysis (PCA) placed them into separate groups. The results allow for proposing that formation of the organohalogenated species involved the fast penetration of bromine into the humic matter molecules and, further, their oxidative destruction by active chlorine.     

Optimization and evaluation of atomic emission gas chromatographic detection for nitrogen using the 388 nm molecular emission spectral band

Nitrogen determination by gas chromatography with atomic emission (microwave-induced plasma) detection (GC-AED) has been accomplished using the 174 nm atomic emission line, but with very limited selectivity and sensitivity. Nitrogen can also be detected using the cyanogen (CN) molecular band at 388 nm. A commercial GC-AED system was modified to allow the use of the 388 nm line for nitrogen detection, giving an improvement of 100-fold in sensitivity and selectivity, when compared with the 174 nm mode. Limits of detection of 10 pg/s were common, representing a 10-fold improvement. Compound-independent behavior was found for the system, working with optimum operating conditions, while instrumental problems were clearly reflected by a drastic compound dependent behavior. Response factors showed an important dependency upon the concentration of the element present. This dependency affected the accuracy of the determination of empirical formulae using GC-AED.     

Standards and GC-MS analysis: An answer to the requirement of compound confirmation

Summary The attribution of an unknown GC-MS chromatographic peak to a specific substance should be confirmed whenever possible by comparison with a standard compound analysed under the same experimental conditions. The range of chemicals supplied by various companies is very wide but can never be completely comprehensive. This paper proposes two simple ways by which a reference compound may be obtained. Firstly, it may occur as an impurity in a commercial sample as a synthesis by-product. Alternatively, the compound may be synthesized by a simple procedure, preferably a single step one, by putting small amounts of reagents in a sealed glass vial placed in a programmable oven. Examples of these two approaches are described.