Chromatography-negative Chemical Ionization Mass Research Articles

Development and validation of a method for the analysis of halophenols and haloanisoles in cork bark macerates by stir bar sorptive extraction heart-cutting two-dimensional gas chromatography negative chemical ionization mass spectrometry

A method has been developed for the quantitative determination in cork bark macerates of 7 halophenols and 5 haloanisoles with demonstrated or suspected contribution to the cork taint off-flavour. Macerates were extracted with stirbar (20 mm polydimethylsiloxane-coated) sorptive extraction under optimized conditions (pH 3.5, 20% NaCl and 60 min). The bars were analysed by automated thermal desorption, heart-cutting two-dimensional gas chromatography and negative chemical ionization-mass spectrometry. Matrix effects were compensated for by a “matrix matched” calibration curve. Limits of detection were in the range 0.03-0.24 ng L−1, below the corresponding odor thresholds. Linearity (0.983 ≤ R2 ≤ 0.998), intra- and inter-day precision (5.4-14.3%) and accuracy (89–126%) were satisfactory. The analysis of 48 natural cork bark samples affected/not-affected bya cryptogamic disease (yellow spot) revealed compositional differences in 2,4,6-trichloroanisole (2,4,6-TCA), 2,4,6-trichlorophenol (2,4,6-TCP) and also in 2,6-dibromophenol, 2,3,4- and 2,4,5-TCP, 2,3,4-TCA and 2,3,4,6-tetrachlorophenol (2,3,4,6-TeCP). In addition, the contents of 2,4,6-TCP and 2,4,6-TCA, and 2,3,4,6-TeCP and some TCPs presented strong linear correlations.

Derivatization gas chromatography negative chemical ionization mass spectrometry for the analysis of trace organic pollutants and their metabolites in human biological samples.

Gas chromatography negative chemical ionization mass spectrometry (GC-NCI-MS) is a preferred instrumental approach for the trace and ultra-trace analysis of various toxic organics and their metabolites in human biological fluids. Specifically, the method has played an important role in the highly sensitive and specific quantitative detection of persistent highly halogenated compounds in environmental matrices and biota during the past few decades. However, for the analysis of toxic metabolites with active hydrogen atoms, such as acids, alcohols, and phenolic compounds, from biological matrixes or organics without electronegative atoms or groups, a derivatization step is often needed prior to GC analysis. Such derivatization aims to change the properties of targets to improve their separation, increase their volatility, and enhance the sensitivity of instrumental detection. This review summarizes three derivatization strategies commonly used for GC methods, i.e., alkylation, silylation, and acylation, together with their application combined with GC-NCI-MS for the high sensitivity analysis of toxic organic metabolites in the human body. The advantages and disadvantages of each derivatization method and potential directions for future applications are discussed. Given the broad variety of applications as well as the compound-specific sensitivity for the ultra-trace analysis of target xenobiotics in human biological fluids, subsequent studies are required to develop convenient, faster derivatization procedures and reagents better suited for routine analysis. Graphical abstract.

Analysis of Perfluorooctanesulfonate Isomers and Other Perfluorinated Alkyl Acids in Serum by In-Port Arylation Gas Chromatography Negative Chemical Ionization–Mass Spectrometry

Perfluorooctanesulfonate (PFOS) is a common environmental pollutant and has been detected in various environmental media. Several major isomers have been identified, and their profiles provide important signatures from the source of contamination. Gas chromatography has a significant resolving power for the isomers. However, methods for derivatizing sulfonates for a sensitive analysis are limited. In this study, in-port derivatization with diaryl iodonium salts into aryl sulfonates was used. A technical mixture of PFOS was separated on gas chromatography to afford 11 isomers. In electron-capture negative ionization, the PFOS derivatives form specific fragmented anions (sulfinate anions). The derivatization was also applied to other per- or polyfluoroalkyl acids (PFASs; 13 perfluoroalkyl carboxylic acids and 10 sulfonates). Analysis of human serum samples was achieved with as little as 50 μL of sample and indicated the presence of PFOS isomers and PFASs. The detection limits of PFOS isomers were 0.02–0.09 ng mL–¹ with sufficient recoveries (85%–98%), and those for other PFASs ranged from 0.01–1 ng mL–¹ (recoveries, 80%–100%), which are suitable for the analysis of human serum samples.

Determination of organochlorine pesticides (OCPs) in breast milk from Rio Grande do Sul, Brazil, using a modified QuEChERS method and gas chromatography-negative chemical ionisation-mass spectrometry

ABSTRACTThe food chain is the main source of exposure to humans by organochlorine pesticides (OCPs) due to the bioaccumulation. Breast milk can accumulate OCPs, so this matrix is often used as an environmental bioindicator. The currently available methods for the determination of several OCPs and metabolites in breast milk involve, in general, multi-step sample preparation and quantification techniques with low selectivity, high cost and much time and labour. Thus, a fast and efficient method based on sample preparation using the quick, easy, cheap, effective, rugged and safe (QuEChERS) method combined with gas chromatography coupled to mass spectrometry with negative chemical ionisation (GC-NCI-MS) was developed, validated and applied for determination of 16 OCPs and metabolites in breast milk samples. The extract was cleaned by dispersive solid-phase extraction (d-SPE) using MgSO4 and C18, evaporated in a Turbovap® system, redissolved and analysed by GC-NCI-MS. The method was validated showing acceptable recoveries (72–118%) and precision (RSD <19%). Method limits of detection (LODs) and quantification (LOQs) ranged from 0.75 to 7.5 ng g−1 and from 2.5 to 25 ng g−1 lipid, respectively. The method was successfully applied to 20 samples of breast milk from different regions of the Rio Grande do Sul state, Brazil, of which 75% contained residues below the LOQs.

Analysis of 7 Dinitroaniline Residues in Complex Food Matrices by GC–NCI/MS

A modified quick, easy, cheap, effective, rugged, and safe sample preparation method combined with gas chromatography–negative chemical ionization–mass spectrometry (GC–NCI/MS) has been developed for the determination of 7 dinitroaniline herbicide residues in complex matrices (garlic, olive oil, scallion, leek and chili). Dinitroaniline residues were extracted with hexane-saturated acetonitrile. After the cleanup with the dispersive solid-phase extraction, the extract was analyzed by GC–NCI/MS in selected ion monitoring mode. Two isotope internal standards (trifluralin-d 14 and pendimethalin-d 5) were employed for quantification. Compared with electron ionization (EI) mode, the superiorities of NCI in sensitivity and selectivity were investigated. Limits of the detection of 7 dinitroanilines were in the range of 0.014–0.096 μg kg−1, and there were no interfering peaks (unlike in EI) in the complex matrices. Recoveries of 7 dinitroanilines in five matrices at three spiked levels (10, 20 and 40 μg kg−1) ranged from 61 to 126 % and the relative standard deviations were all below 12 %.

The human body burden of polybrominated diphenyl ethers and their relationships with thyroid hormones in the general population in Northern China

This study was conducted to determine the human body burden of polybrominated diphenyl ethers (PBDEs) and then clarify the relationships between that and the disruption of thyroid hormones in the general population in Northern China. Between November 2010 and May 2011, 124 serum samples were obtained from volunteers from the provinces of Shanxi and Liaoning. Serum samples were prepared by solid-phase extraction and analyzed for BDE-17, 28, 47, 66, 99, 100, 153, 154, 183 and 209 by gas chromatography–negative chemical ionization mass spectrometry. The median concentration of the total PBDEs was 7.2ng/g lipid weights (lw); concentrations ranged from 2.1 to 160.3ng/glw. The PBDE profiles in this study differed from those of other general populations. BDE-209 was the most abundant congener (median, 5.0ng/glw; range, non-detected — 157.1ng/glw), accounting for more than 75% of the total PBDEs, followed by BDE-153. The total PBDE concentrations in men were significantly higher as compared to women. The donors' age was correlated with a few PBDE congeners, but was not correlated with the total PBDE concentrations. The overall level of PBDEs in this study was lower than that observed in general populations in Southern China, Europe, and North America. There were apparent correlations between concentrations of several PBDE congeners and thyroid hormones. Triiodothyronine (T3) was correlated with BDE-99 and 209 and inversely correlated with BDE-17, 28, 47, 153, 183, and the summed tri- to hepta-PBDE congeners (∑3–7PBDEs). Thyroid-stimulating hormone (TSH) was correlated with BDE-17, 28, 47, and 183 and inversely correlated with BDE-99. No correlation between free tetraidothyronine (FT4) and PBDEs was observed. Logistic regression analysis results indicated that those with higher levels of BDE-17 or BDE-153 had significantly lower odds of having T3 levels above the normal range compared to those with lower levels of BDE-17 or BDE-153. Association between FT4 and BDE-153 disappeared after controlling for sex and age. However, there was no significant association between TSH and PBDEs. The results of the present study showed that even at a relatively low level, PBDEs might interfere with the thyroid hormone levels in the general population.

A multi-residue method for pesticides analysis in green coffee beans using gas chromatography–negative chemical ionization mass spectrometry in selective ion monitoring mode

In this study, a new gas chromatography–mass spectrometry (GC–MS) method, using the very selective negative chemical ionization (NCI) mode, was developed and applied in combination with a modified acetonitrile-based extraction method (QuEChERS) for the analysis of a large number of pesticide residues (51 pesticides, including isomers and degradation products) in green coffee beans. A previously developed integrated sample homogenization and extraction method for both pesticides and mycotoxins analysis was used. An homogeneous slurry of green milled coffee beans and water (ratio 1:4, w/w) was prepared and extracted with acetonitrile/acetic acid (1%), followed by magnesium sulfate addition for phase separation. Aliquots from this extract could be used directly for LC–MS/MS analysis of mycotoxins and LC-amenable pesticides. For GC–MS analysis, a further clean-up was necessary. C18- and PSA-bonded silica were tested as dispersive solid-phase extraction (d-SPE) sorbents, separate and as a mixture, and the best results were obtained using C18-bonded silica. For the optimal sensitivity and selectivity, GC–MS detection in the NCI-selected ion monitoring (SIM) mode had to be used to allow the fast analysis of the difficult coffee bean matrix. The validation was performed by analyzing recovery samples at three different spike concentrations, 10, 20 and 50μgkg−1, with 6 replicates (n=6) at each concentration. Linearity (r2) of calibration curves, estimated instrument and method limits of detection and limits of quantification (LODi, LODm, LOQi and LOQm, respectively), accuracy (as recovery %), precision (as RSD%) and matrix effects (%) were determined for each individual pesticide. From the 51 analytes (42 parent pesticides, 4 isomers and 5 degradation products) determined by GC–MS (NCI-SIM), approximately 76% showed average recoveries between 70–120% and 75% and RSD≤20% at the lowest spike concentration of 10μgkg−1, the target method LOQ. For the spike concentrations of 20 and 50μgkg−1, the recoveries and RSDs were even better. The validated LOQm was 10, 20 and 50μgkg−1 for respectively 33, 3 and 6 of the analytes studied. For five compounds, the European Union method performance requirements for the validation of a quantitative method (average recoveries between 70-120% and repeatability RSD≤20%) were not achieved and 4 problematic pesticides (captan, captafol, folpet and dicofol) could not be detected as their parent compound, but only via their degradation products. Although the matrix effect (matrix-enhanced detector response) was high for all pesticides studied, the matrix interference was minimal, due to the high selectivity obtained with the GC–NCI-MS detection. Matrix-matched calibration for applying the method in routine analysis is recommended for reliable quantitative results.

Polybrominated diphenyl ether levels in wild and farmed Chilean salmon and preliminary flow data for commercial transport

AbstractThis pilot study documented the occurrence and levels of brominated flame retardants in the tissues of farmed and wild salmon in southern Chile. Samples of Coho salmon and rainbow trout were obtained from fish farms, rivers and lakes in the Patagonia in Aysen Region, Chile. The samples were analyzed by Gas Chromatography Negative Chemical Ionization Mass Spectrometry for the different polybrominated diphenyl ether (PBDE) congeners. Contaminants were observed in all the samples, and the congeners BDE 17, 28, 47 and 66 were observed in all both farmed and wild samples. The concentrations were higher in the farmed Coho salmon, presenting significant differences with wild salmon. The levels reached 182 pg/g wet weight (ww) vs. 120 ww. In the case of the rainbow trout, the concentrations were lower, although the congener profile was quite similar. The levels reached an average of 100 pg/g ww in the farmed fish versus 110 pg/g ww in wild fish, and no significant difference was observed between the species. In both species, the congener with the highest concentration was BDE 47. Based on this information, the BDE flow was estimated for commerce, which is a form of pollutant transport not usually considered in POP pollution studies. A preliminary estimation indicated that the quantity of PBDEs mobilized by commerce was in the order of kg, and in the case of Chile might reach almost 1 kg.

Method optimization to measure polybrominated diphenyl ether (PBDE) concentrations in soils of Bratislava, Slovakia

We modified an analytical method to determine polybrominated diphenyl ethers (PBDEs) in urban soils of Bratislava (Slovakia). Gel permeation chromatography (GPC) introduced as a clean-up step for soil extracts substantially reduced matrix enhancements when PBDEs were measured with gas chromatography–negative chemical ionization–mass spectrometry (GC–NCI–MS). The resulting method proved to be accurate, precise, and showed low detection limits. The sum of 15 PBDE concentrations in surface horizons of Bratislava soils ranged from 87 to 627 pg g −1. PBDE concentrations were mostly higher in surface than deeper horizons probably because of atmospheric deposition and lack of substantial vertical transport. Lower brominated PBDEs undergo more soil–atmosphere exchanges or are more scavenged and transferred with litter fall to the soil organic matter than higher brominated ones as suggested by the correlation between lower brominated PBDEs and soil organic C (C org) concentrations.

11-Nor-Δ 9-tetrahydrocannabinol-9-carboxylic acid ethyl ester (THC-COOEt): Unsuccessful search for a marker of combined cannabis and alcohol consumption

11-Nor-Δ 9-tetrahydrocannabinol-9-carboxylic acid ethyl ester (THC-COOEt) can be presumed to be a mixed metabolite formed during combined consumption of cannabinoids and alcohol. In order to examine this hypothesis, THC-COOEt and its deuterated analogue D 3-THC-COOEt were synthesized as reference substance and internal standard from the corresponding carboxylic acids and diazoethane and methods were developed for the sensitive detection of THC-COOEt in plasma and hair based on gas chromatography–electron impact mass spectrometry after silylation with N-methyl- N-tert-butyldimethylsilyl-trifluoroacetamide and gas chromatography–negative chemical ionization mass spectrometry (GC-NCI-MS) as well as tandem mass spectrometry (GC-NCI-MS-MS) after derivatization with pentafluoropropionyl anhydride. The methods were applied for THC-COOEt determination to plasma samples from 22 drunk driving cases which contained both ethanol (0.30–2.16 mg/g) and THC-COOH (15–252 ng/mL) as well as to 12 hair samples from drug fatalities which were both positive for THC (0.09–2.04 ng/mg) and fatty acid ethyl esters as markers of chronic alcohol abuse (0.70–6.3 ng/mg). In none of these samples THC-COOEt could be found with limits of detection of 0.3 ng/mL in plasma and 2 pg/mg in hair in 11 samples using GC-NCI-MS and 0.2 pg/mg in one sample using GC-NCI-MS. Therefore, the use of this compound as a marker for combined cannabis and alcohol consumption could not be achieved.

Determination of hydroxylated metabolites of polycyclic aromatic hydrocarbons in human hair by gas chromatography–negative chemical ionization mass spectrometry

The study describes the determination of mono-hydroxylated polycyclic aromatic hydrocarbons (OH-PAHs), metabolites of PAHs, in human hair. Twelve selected OH-PAHs from two to four rings, generally determined in urine analysis, were investigated as markers of human exposure to PAHs. Following hydrolysis of hair specimens of 50–300 mg with 1 M NaOH, OH-PAHs were extracted using dichloromethane and submitted to an optimized derivatization with (2S,4R)-N-heptafluorobutyryl-4-heptafluorobutoyloxy-prolyl chloride. Compounds were then analyzed using gas chromatography–negative chemical ionization mass spectrometry (GC–NCIMS). The average inter-day and intra-day variability was 12% and 17%, respectively. The average recovery was 52% and the limits of detection and quantification ranged from 20 and 66 pmol/g for 1-OH-phenanthrene (i.e., 3.9 and 12.8 pg/mg) to 311 and 1030 pmol/g for 2-OH-benzo(c)phenanthrene (i.e., 75.9 and 251 pg/mg). The influence of hair washing with water as decontamination step, and enzymatic treatment (β-glucuronidase) to hydrolyze conjugated derivatives were also tested. The application of the developed method to the analysis of 30 hair specimens (17 from non-smoker and 13 from smoker volunteers) demonstrated inter-individual qualitative and quantitative variations. According to the easiness of hair sampling and based on the extended detection windows provided by hair analysis, this method is proposed as a new promising tool for the assessment of human chronic exposure to PAHs.

Determination of phenolic endocrine disrupting chemicals and acidic pharmaceuticals in surface water of the Pearl Rivers in South China by gas chromatography–negative chemical ionization–mass spectrometry

An analytical method for phenolic endocrine disrupting chemicals and acidic pharmaceuticals in river water was developed using gas chromatography mass spectrometry (GC–MS) coupled with negative chemical ionization (NCI) technique, and used for the determination of these compounds in the Pearl Rivers (Liuxi, Zhujiang and Shijing Rivers). Derivatization using pentafluorobenzoyl chloride (PFBOCl) and pentafluorobenzyl bromide (PFBBr) before GC–MS analysis were applied and optimized for phenolic compounds and acidic compounds, respectively. The target compounds were analyzed for river waters from the upstream to downstream of the Pearl Rivers. Phenolic compounds 4- tert-octylphenol (4- t-OP), 4-nonylphenol (4-NP), bisphenol-A (BPA), estrone (E1), estradiol (E2) and triclosan (TCS) were detected at trace or low levels in the water samples from Liuxi River and Zhujiang River. Diethylstilbestrol (DES) was not detected in the Pearl Rivers. The highest concentrations of the phenolic compounds were found in Shijing River, and they were 3150 ng/L for 4- t-OP, 11,300 ng/L for 4-NP, 1040 ng/L for BPA, 79 ng/L for E1, 7.7 ng/L for E2 and 355 ng/L for TCS, respectively. Only a few acidic pharmaceuticals were detected at low concentrations in water from Liuxi River and Zhujiang River, but the highest concentrations for the acidic pharmaceuticals were also found in Shijing River. The highest concentrations detected for clofibric acid, ibuprofen, gemfibrozil, naproxen, mefenamic acid and diclofenac were 17 ng/L, 685 ng/L, 19.8 ng/L, 125 ng/L, 24.6 ng/l and 150 ng/L, respectively. The results suggest Liuxi and Zhujiang Rivers are only slightly contaminated and can be used as drinking water sources, but Shijing River is heavily polluted by the wastewater from nearby towns.

Gas chromatography negative ion chemical ionization mass spectrometry: Application to the detection of alkyl nitrates and halocarbons in the atmosphere

Alkyl nitrates and very short-lived halocarbon species are important atmospheric trace gas species that are present in the low to sub parts per trillion concentration range. This presents an analytical challenge for their detection and quantification that requires instrumentation with high sensitivity and selectivity. In this paper, we present a new in situ gas chromatograph negative ion chemical ionization mass spectrometer (GC/NICI–MS) coupled to a non-cryogen sample pre-concentration system. This instrument, with detection limits of <0.01 ppt, is capable of detecting and quantifying a large suite of alkyl nitrate and halocarbon species with high sensitivity and precision. The effects of ion source temperature and reagent gas pressure on the ionization efficiency of the NICI mode are investigated and the results are used to optimize the sensitivity. The NICI mode is compared to the more frequently used electron impact (EI) ionization and the enhancements in sensitivity are presented for all the calibrated compounds.

Analysis of aldehydes in excipients used in liquid/semi-solid formulations by gas chromatography–negative chemical ionization mass spectrometry

Monitoring of low-molecular-weight aldehyde levels in excipients used in liquid/semi-solid based capsule (LFC) dosage forms plays a critical role in the development of these pharmaceutical products. A simple, sensitive and specific method based on gas chromatography coupled with mass spectrometry (GC–MS) utilizing an Rtx-5MS capillary column was developed and validated for the detection and quantification of C 1–C 8 aliphatic aldehydes in LFC excipients at sub-μg/g levels. The proposed procedure is based on the derivatization of aldehydes in 10:1 (v/v) acetonitrile:water with O-2,3,4,5,6-(pentafluorobenzyl) hydroxylamine hydrochloride (PFBHA), followed by direct GC analysis of aldehyde-PFBHA-oxime derivatives with negative chemical ionization (NCI) MS detection. The method developed was successfully applied to the analysis of short chain aldehydes in 30 typical LFC excipients. An example case study on the formation and growth of aldehydes in these excipients under accelerated storage conditions is also reported.

Quantification of low levels of organochlorine pesticides using small volumes (≤100 μl) of plasma of wild birds through gas chromatography negative chemical ionization mass spectrometry

A solid phase extraction and gas chromatography with negative chemical ionization mass spectrometry in scan mode (GC-NCI-MS) method was developed to identify and quantify for the first time low levels of organochlorine pesticides (OCs) in plasma samples of less than 100 μl from wild birds. The method detection limits ranged from 0.012 to 0.102 pg/μl and the method reporting limit from 0.036 to 0.307 pg/μl for α, γ, β and δ-hexachlorocyclohexane (HCH), heptachlor, aldrin, heptachlor epoxide, endosulfan I, 1,1-dichloro-2,2-bis( p-chlorophenyl)ethylene ( p, p′-DDE), dieldrin, endrin, endosulfan-II, endrin-aldehyde and endosulfan-sulfate. Pesticide levels in small serum samples from individual Falco sparverius, Sturnella neglecta, Mimus polyglottos and Columbina passerina were quantified. Concentrations ranged from not detected (n/d) to 204.9 pg/μl for some OC pesticides. All levels in the food web in and around cultivated areas showed the presence of pesticides notwithstanding the small areas for agriculture existing in the desert of Baja California peninsula.

Automated analysis of 2-methyl-3-furanthiol and 3-mercaptohexyl acetate at ng L −1 level by headspace solid-phase microextracion with on-fibre derivatisation and gas chromatography–negative chemical ionization mass spectrometric determination

A fast and automated method for the analysis at ng L −1 level of aroma-powerful polyfunctional thiols has been developed and applied to wine. The sample is just poured in a 20 mL vial and its vapour extracted with a poly(dimethylsiloxane)–divinylbenzene (PDMS–DVB) solid-phase microextraction fibre (65 μm thickness) previously exposed to vapours of the reactive (pentafluorobenzyl bromide) and of an alkali (tributylamine). The derivatised compounds are subsequently desorbed in the GC system and determined by negative chemical ionization mass spectrometry. The method is fully automated by using a Combi-Pal autosampler conveniently programmed. The analysis takes 50 min, which contrasts to the long and tedious methods previously proposed. The development of an optimal procedure is constrained by the aggressive character of the reagent (towards the fibre and the chromatographic column), its volatility and the quality of the blanks that can be obtained. Therefore, a critical step was fixing in the fibre a “safe” and repetitive amount of reagent. This was achieved by exposing the fibre (5 min) to the vapours of a water:acetone (9:1) solution containing 200 mg L −1 of reagent. Under these conditions, the extraction-derivatisation of analytes improves with time and temperature, and the best working conditions are dictated by a compromise between sensitivity, speed and chromatographic performance. Although analytes studied were 2-methyl-3-furanthiol, 4-mercapto-4-methyl-2-pentanone, 3-mercaptohexanol, 2-furanmethanethiol and 3-mercaptohexyl acetate, a good analytical performance could be achieved only for these two last compounds. Both of them can be repetitively (10% < RSD < 20%) determined in wine at concentrations below 0.1 ng L −1. Other aspects considered in the method setup were the oxidation of analytes during the process, and the electron-capture detection (ECD) and MS properties of the pentafluorobenzyl derivatives of different polyfunctional thiols.

Reduction of brain lipid peroxidation by CSF drainage in Alzheimer's disease patients.

Alzheimer's disease (AD) is associated with an increase in cerebrospinal fluid (CSF) levels of the isoprostane 8,12-iso-iPF2alpha-VI, a specific marker of in vivo lipid peroxidation. Poor cerebral clearance of end products of oxidative reactions via CSF circulation may contribute to and sustain ongoing stress. CSF drainage via a low-flow ventriculoperitoneal (VP) shunt may improve removal of these products, reducing oxidative stress. We quantified this biomarker in patients with AD undergoing to VP shunt placement at baseline and after one-year period. CSF sampling occurred at baseline and quarterly visits for one year. Levels of this isoprostane were determined simultaneously at the end of the study by gas chromatography negative ion chemical ionization mass spectrometry. Over one-year, CSF 8,12-iso-iPF2alpha-VI levels consistently decreased versus baseline (51% of initial level), while CSF protein, glucose, cell count and IgG concentrations remained within normal limits. This finding supports the hypothesis that improving CSF drainage enhances extra-cellular clearance of end products of oxidative reactions and lowers brain lipid peroxidation.

Determination of picogram levels of midazolam, and 1- and 4-hydroxymidazolam in human plasma by gas chromatography–negative chemical ionization–mass spectrometry

Midazolam is a widely accepted probe for phenotyping cytochrome P4503A. A gas chromatography–mass spectrometry (GC–MS)–negative chemical ionization method is presented which allows measuring very low levels of midazolam (MID), 1-OH midazolam (1OHMID) and 4-OH midazolam (4OHMID), in plasma, after derivatization with the reagent N- tert-butyldimethylsilyl- N-methyltrifluoroacetamide. The standard curves were linear over a working range of 20 pg/ml to 5 ng/ml for the three compounds, with the mean coefficients of correlation of the calibration curves ( n=6) being 0.999 for MID and 1OHMID, and 1.0 for 4OHMID. The mean recoveries measured at 100 pg/ml, 500 pg/ml, and 2 ng/ml, ranged from 76 to 87% for MID, from 76 to 99% for 1OHMID, from 68 to 84% for 4OHMID, and from 82 to 109% for N-ethyloxazepam (internal standard). Intra- ( n=7) and inter-day ( n=8) coefficients of variation determined at three concentrations ranged from 1 to 8% for MID, from 2 to 13% for 1OHMID and from 1 to 14% for 4OHMID. The percent theoretical concentrations (accuracy) were within ±8% for MID and 1OHMID, within ±9% for 4OHMID at 500 pg/ml and 2 ng/ml, and within ±28% for 4OHMID at 100 pg/ml. The limits of quantitation were found to be 10 pg/ml for the three compounds. This method can be used for phenotyping cytochrome P4503A in humans following the administration of a very low oral dose of midazolam (75 μg), without central nervous system side-effects.

Volatile fatty acids as malodorous compounds in wool scouring water and lanolin. Origin and characterisation

Volatile fatty adds (C2‐C7) analysis in wool scouring water and lanolin is presented. These substances are of major interest as malodorous compounds in urban and industrial wastewaters. In this work, they have been analysed in wool scouring water by headspace solid‐phase microextraction followed by gas chromatography negative chemical ionisation mass spectrometry. Most of the volatile fatty adds have been identified at μg g−1 levels. In addition, since lanolin is a major impurity of raw wool, volatile fatty add patterns of wool scouring water and lanolin have been compared in order to establish the origin of these compounds in the wastewater. Finally, the efficiency of the deodorization step, mandatory to obtain commerdal lanolin, has been assessed taking into account the decrease in volatile fatty add content from the raw wool to the lanolin.

Solid-phase extraction versus solid-phase microextraction for the determination of chlorinated paraffins in water using gas chromatography–negative chemical ionisation mass spectrometry

Solid-phase extraction (SPE) and solid-phase microextraction (SPME) were evaluated for the analysis of short-chain chlorinated paraffins (SCCPs) in water samples using gas chromatography coupled to negative chemical ionisation mass spectrometry (GC-NCI-MS). For SPE optimisation, four commercially available SPE cartridges were tested and several SPE parameters, such as the elution solvent, elution volume and breakthrough volume were studied. The best results were obtained with Varian Bond Elut-C 18. In order to achieve a high selectivity in the determination of SCCPs, GC-NCI-MS was used. Quality parameters of the optimised SPE and SPME procedures were determined, and the best results were obtained for the SPE/GC-NCI-MS method with LODs of 5 and 20 ng l −1 for tap and river water, respectively. This method was successfully applied to the analysis of SCCPs in river water samples at concentrations below the μg l −1 level.