Tin, Titanium, Tantalum, Vanadium and Niobium Oxide Based Sensors to Detect Colorectal Cancer Exhalations in Blood Samples.

User-friendly, low-cost equipment for preventive screening of severe or deadly pathologies are one of the most sought devices by the National Health Services, as they allow early disease detection and treatment, often avoiding its degeneration. In recent years more and more research groups are developing devices aimed at these goals employing gas sensors. Here, nanostructured chemoresistive metal oxide (MOX) sensors were employed in a patented prototype aimed to detect volatile organic compounds (VOCs), exhaled by blood samples collected from patients affected by colorectal cancer and from healthy subjects as a control. Four sensors, carefully selected after many years of laboratory tests on biological samples (cultured cells, human stools, human biopsies, etc.), were based here on various percentages of tin, tungsten, titanium, niobium, tantalum and vanadium oxides. Sensor voltage responses were statistically analyzed also with the receiver operating characteristic (ROC) curves, that allowed the identification of the cut-off discriminating between healthy and tumor affected subjects for each sensor, leading to an estimate of sensitivity and specificity parameters. ROC analysis demonstrated that sensors employing tin and titanium oxides decorated with gold nanoparticles gave sensitivities up to 80% yet with a specificity of 70%.

Impact of stressors in the aviation environment on xenobiotic dosimetry in humans: physiologically based prediction of the effect of barometric pressure or altitude.

Standard health risks from volatile organic compounds (VOCs) are generally interpreted at ambient environmental conditions. The aim of this study was to develop a strategy for using physiologically based pharmacokinetic (PBPK) modeling to compare known risks in the general population to calculated risks in pilots experiencing pressure-based stressors. PBPK models facilitate these comparisons by prediction of how target-tissue specific doses are altered when a stressor, such as high altitude, produces changes in physiological parameters. Cardiac output, regional blood flow, and alveolar ventilation rate following acute exposure to altitude ranging from moderate to extremely high were estimated from published data from 52 groups of human subjects. Scenarios where pilots might inhale toluene, 1,2,4-trimethylbenzene (1,2,4-TMB), or cyclohexane during routine military flight training were simulated. At the recommended Threshold Limit Values (TLV), arterial blood concentrations were predicted to be higher for exposure at 15000 ft (4572 m) than at sea level. The differences were greater for toluene and TMB, which have higher blood: air and fat: blood partition coefficients than less lipophilic cyclohexane. In summary, quantitative approaches to internal dosimetry prediction that take advantage of existing knowledge of physiological changes induced by occupational stressors possess potential as tools in performing a human health risk assessment.

Area under the blood concentration-time curve (AUC) of ethylbenzene concentration in rats: relationship to inhalation and oral administration route-dose.

For human risk assessment of toxic chemicals, especially volatile organic compounds (VOCs), the Ministry of the Environment, Government of Japan, has called for the interconversion of inhalation-dose and oral-dose data, two common exposure routes. To address this issue, the present study investigated the time-course changes of ethylbenzene (EB) concentrations in the blood of rats during and after 6-hr inhalation exposure to EB (25, 50, 100, and 200 ppm) and after oral administration of EB by a single oral gavage (25, 50, 100, and 200 mg/kg) of EB. The Area Under the blood concentration-time Curve (AUC) at each blood collection time point (0, 30, 60, 120, 180, 360, 420, 540, and 1440 min, after starting exposure) was determined. The inhalation dose of 25 ppm corresponded closely to the oral administration of 25 mg/kg・bw (r value of 0.859), and the inhalation dose of 200 ppm correlated with the oral administration of 100 mg/kg・bw (r value of 0.948). These results suggest that this comparison using the AUC data at each blood collection time point is valuable for understanding the route- and dose-effects of EB. This study will improve risk assessment of human exposure to EB and other VOCs.

Biological and environmental exposure monitoring of volatile organic compounds among nail technicians in the Greater Boston area.

Nail technicians are exposed to volatile organic compounds (VOCs) from nail products, but no studies have previously measured VOC biomarkers for these workers. This study of 10 nail technicians aimed to identify VOCs in nail salons and explore relationships between air concentrations and biomarkers. Personal and area air samples were collected using thermal desorption tubes during a work shift and analyzed using gas chromatography/mass spectrometry (GC/MS) for 71 VOCs. Whole blood samples were collected pre-shift and post-shift, and analyzed using GC/MS for 43 VOCs. Ventilation rates were determined using continuous CO2 measurements. Predominant air VOC levels were ethyl methacrylate (median 240 µg/m3 ), methyl methacrylate (median 205 µg/m3 ), toluene (median 100 µg/m3 ), and ethyl acetate (median 639 µg/m3 ). Blood levels were significantly higher post-shift than pre-shift for toluene (median pre-shift 0.158 µg/L and post-shift 0.360 µg/L) and ethyl acetate (median pre-shift <0.158 µg/L and post-shift 0.510 µg/L); methacrylates were not measured in blood because of their instability. Based on VOCs measured in these seven nail salons, we estimated that emissions from Greater Boston area nail salons may contribute to ambient VOCs. Ventilation rates did not always meet the ASHRAE guideline for nail salons. There is a need for changes in nail product formulation and better ventilation to reduce VOC occupational exposures.

A cross-sectional survey based on blood VOCs, hematological parameters and urine indicators in a population in Jilin, Northeast China.

The objective of this study was to examine whether long-term exposure to low-dose volatile organic compounds (VOCs) will have an effect on the health of non-occupational population. A total of 499 non-occupational participants aged more than 18 that live around Jilin Petrochemical Industrial Zone were chosen by stratified cluster random sampling. Their blood VOCs' levels, hematological parameters and urine indicators together with detailed questionnaire data were used to find possible relationships using binary logistic regression analysis. The detection rate of benzene in the blood was high in the non-occupational population around the industrial area, and it even reached 82.3% in males but no significant difference was recorded between male and female population. In addition, trichloroethane (male: 33.2% V female: 21.7%; p = 0.002), carbon tetrachloride (males: 20.3% V females: 7.5%; p < 0.001) and trichlorethylene (male: 34.9% V female: 24.7%; p = 0.004) all showed significant differences in gender, and without exception, the prevalence of males was higher in these three VOCs than of females. The changes in red blood cell (RBC), hematocrit (HCT) and basophils are correlated with carbon tetrachloride, trichloroethylene and chloroform, respectively. And RBC, HCT and basophils are statistically significant in male compared with female of the study population. The increase in trichlorethylene was associated with an increase of 1.723% (95% CI 1.058-2.806) in HCT. The increase in carbon tetrachloride showed a more significant correlation with an increase of 2.638% in RBC count (95% CI 1.169-5.953). And trichloromethane led to a 1.922% (95% CI 1.051-3.513) increase in basophils. The changes in urinary WBC, urine ketone (KET) and urinary bilirubin (BIL) showed significant correlation with benzene, carbon tetrachloride and dibromochloromethane, respectively. The correlation in females is more significant than in males. The increase of benzene in the female population increased urinary leukocyte count by 2.902% (95% CI 1.275-6.601). The effect of carbon tetrachloride on KET was particularly pronounced, resulting in an increase of 7.000% (95% CI 1.608-30.465). Simultaneously, an increase in dibromochloromethane caused an increase of 4.256% (95% CI 1.373-13.192) in BIL. The changes in RBC, HCT and basophils can only serve as an auxiliary indicator for disease diagnosis, so they have no significant clinical significance. However, the alteration of urinary WBC, KET and BIL has great clinical significances, and it is suggested that the monitoring of the above indicators from low-dose long-term exposure be strengthen in this area.

Assessing Human Exposure to Organic Pollutants in the Indoor Environment.

There is an ongoing probing of the role of chemicals in the indoor environment. The majority of potential target substances are so-called very volatile, volatile, and semi-volatile organic compounds (VVOCs, VOCs, and SVOCs). Depending on their physical properties and the mass transfer conditions, they are distributed in or between the gas phase, particle phase, settled house dust, surface films, clothing, and other fabrics as well as the exposed skin and hair of the occupants themselves. Therefore, inhalation, ingestion, and dermal uptake all must be considered as relevant pathways for exposure assessment in human habitats. Exposure to VVOCs, VOCs, and SVOCs can be estimated by measuring their concentrations in relevant indoor compartments or by determining the amounts of the target compounds and/or their metabolites in urine and blood. Assessing the various routes of exposure often requires a combination of sophisticated and interdisciplinary theoretical background and experimental techniques. Consequently, close communication and collaboration between chemical and exposure scientists are needed to achieve a better understanding of human exposure to chemical substances in various indoor environments. Embedded in the toxicological context, this is the basis for assessing the corresponding health risks and for determining control strategies or approaches to limit such risks.

Associations between blood BTEXS concentrations and hematologic parameters among adult residents of the U.S. Gulf States.

BACKGROUND: Studies of workers exposed to benzene at average air concentrations below one part per million suggest that benzene, a known hematotoxin, causes hematopoietic damage even at low exposure levels. However, evidence of such effects outside of occupational settings and for other volatile organic compounds (VOCs) is limited. OBJECTIVE: To investigate associations between ambient exposures to five VOCs, including benzene, and hematologic parameters among adult residents of the U.S. Gulf Coast. MATERIALS AND METHODS: Blood concentrations of selected VOCs were measured in a sample of adult participants in the Gulf Long-term Follow-up Study (GuLF STUDY) during 2012 and 2013. Complete blood counts with differentials were also performed on a subset of participants (n=406). We used these data together with detailed questionnaire data to estimate adjusted associations between blood BTEXS (benzene, toluene, ethylbenzene, o-xylene, m/p-xylene, and styrene) concentrations and hematologic parameters using generalized linear models. RESULTS: We observed inverse associations between blood benzene concentrations and hemoglobin concentration and mean corpuscular hemoglobin concentration, and a positive association with red cell distribution width among tobacco smoke-unexposed participants (n=146). Among tobacco smoke-exposed participants (n=247), we observed positive associations between blood VOC concentrations and several hematologic parameters, including increased white blood cell and platelet counts, suggestive of hematopoietic stimulation typically associated with tobacco smoke exposure. Most associations were stronger for benzene than for the other VOCs. CONCLUSIONS: Our results suggest that ambient exposure to BTEXS, particularly benzene, may be associated with hematologic effects, including decreased hemoglobin concentration, mean corpuscular hemoglobin concentration, and increased red cell distribution width.

Volatile organic compounds in plasma for the diagnosis of esophageal adenocarcinoma: a pilot study.

BACKGROUND AND AIMS: A noninvasive screening test that can detect esophageal adenocarcinoma (EAC) at an earlier stage could improve the prognosis associated with EAC. The role of plasma volatile organic compounds (VOCs) for the diagnosis of EAC has not been previously studied. METHODS: Plasma samples were collected from subjects with EAC and GERD before endoscopy. Twenty-two preselected VOCs were analyzed with selected ion flow tube mass spectrometry. RESULTS: The headspaces from 39 plasma samples (20 EAC, 19 GERD) were analyzed. The levels of 9 VOCs (acetonitrile, acrylonitrile, carbon disulfide, isoprene, 1-heptene, 3-methylhexane, [E]-2-nonene, hydrogen sulfide, and triethylamine) were significantly altered in EAC patients compared with GERD patients. A multivariable logistic regression analysis was performed to build a model for the prediction of EAC. The model identified patients with EAC with an area under the curve of 0.83 (95% confidence interval, 0.67-0.98). CONCLUSIONS: Plasma VOCs may be useful in diagnosing EAC. Larger studies are needed to confirm our pilot study observations.

Selected volatile organic compounds as biomarkers for exposure to tobacco smoke.

Cutoff levels on the scales for benzene, ethylbenzene, toluene, styrene, o-xylene and m/p-xylene in blood were developed to classify smokers from non-smokers. Self-reported smoking during the last 5 d was used as the true smoking status. Receiver operating characteristics methods that minimized the difference between specificity and sensitivity were used to develop these cutoffs. Data from National Health and Nutrition Examination Survey for the cycle 2005-2006 were used for this purpose. For the total population, a cutoff of 0.038 ng/ml for benzene was able to classify smokers from non-smokers with a sensitivity of 83.6% and specificity of 83.7%.

Evaluation and modeling of the impact of coexposures to VOC mixtures on urinary biomarkers.

CONTEXT: Urinary biomarkers are widely used among biomonitoring studies because of their ease of collection and nonintrusiveness. Chloroform and TEX (i.e., toluene, ethylbenzene, and m-xylene) are chemicals that are often found together because of common use. Although interactions occurring among TEX are well-known, no information exists on possible kinetic interactions between these chemicals and chloroform at the level of parent compound or urinary biomarkers. OBJECTIVE: The objective of this study was therefore to study the possible interactions between these compounds in human volunteers with special emphasis on the potential impact on urinary biomarkers. MATERIALS AND METHODS: Five male volunteers were exposed by inhalation for 6 h to single, binary, and quaternary mixtures that included chloroform. Exhaled air and blood samples were collected and analyzed for parent compound concentrations. Urinary biomarkers (o-cresol, mandelic, and m-methylhippuric acids) were quantified in urine samples. Published PBPK model for chloroform was used, and a Vmax of 3.4 mg/h/kg was optimized to provide a better fit with blood data. Adapted PBPK models from our previous study were used for parent compounds and urinary biomarkers for TEX. RESULTS: Binary exposures with chloroform resulted in no significant interactions. Experimental data for quaternary mixture exposures were well predicted by PBPK models using published description of competitive inhibition among TEX components. However, no significant interactions were observed at levels used in this study. CONCLUSION: PBPK models for urinary biomarkers proved to be a good tool in quantifying exposure to VOC.

Diagnosis of bovine tuberculosis using a metal oxide-based electronic nose.

Electronic noses (e-noses) have been used for environmental monitoring, standardization of medicinal flavourings, food safety tests and diagnosis of infectious diseases based on the statistical analysis of volatile organic compounds (VOCs). Bovine tuberculosis (bTB) is officially diagnosed using the intradermal skin test (IST), which is time-consuming and labour-intensive. Therefore, a more convenient and rapid test with greater sensitivity would be advantageous as prescreening test. In this study, we used a metal oxide sensor (MOS) type e-nose to analyse VOCs in a bTB-infected (n = 11) and bTB-free (n = 10) sera, from cattle whose health status was confirmed using the IST, and pathological and bacteriological examinations. The differences in VOCs from bTB-infected and bTB-free sera detected by the e-nose were statistically analysed using principal components and discriminant factor analyses. bTB-infected and bTB-free sera could be discriminated by MOS type e-nose, and analysing time per sample was only 20 min. VOC analysis using a MOS e-nose was a rapid and automated prescreening method to diagnose bTB, and can be used to select bTB-suspect cattle for IST confirmation. Further studies are required to estimate test sensitivity and specificity. Significance and impact of the study: Bovine tuberculosis (bTB) in cattle is diagnosed using the intradermal skin test (IST); however, this method is very time-consuming and labour-intensive. We analysed volatile organic compounds that are obtained from serum using a metal oxide sensor type of electronic nose to discriminate between TB-infected and TB-free sera. This simple and automated technique will be useful to prescreen bTB-suspects and reduce the time and labour required to perform the IST.

Effects of exposure to mixed volatile organic compounds on the neurobehavioral test performance in a cross-sectional study of US adults.

While the environmental exposure to multiple volatile organic compounds (VOCs) is ubiquitous, its neurobehavioral effects are not well understood. We assessed the associations between short-term exposure to VOC mixtures and neurobehavioral test performances on 497 participants in the Third National Health and Nutrition Examination Survey, using quantile and ordinary least squares regression models. We grouped 10 blood VOCs into 3 mixtures based on the principal component analysis, where Mix1 included benzene, toluene, ethylbenzene, m-/p-xylene, o-xylene, and styrene; Mix2 included chloroform and tetrachloroethene; and Mix3 included 1,1,1-trichloroethane and 1,4-dichlorobenzene. We found a general lack of significant adverse effects with exceptions limited to those with the worst performance (i.e. the top 10 percent) in the simple reaction time test, suggesting that these people were potentially more susceptible to impacts of VOC mixtures. However, further research is needed to clarify the neurobehavioral effects of chronic low-level exposure to VOC mixtures among the general population.

Effect of age and storage conditions on the volatile organic compound profile of blood.

Cadaver-detection dogs are used by the police to locate missing persons, victims of homicide, and human remains following mass disasters. Training is conducted using a variety of training aids including blood which can be hours, weeks or months old and stored under variable conditions. The aim of this study was to chemically profile human blood using solid-phase microextraction coupled with gas chromatography-mass spectrometry to determine how the volatile organic compound (VOC) profile changed over time and under variable storage conditions. The VOC profiles of fresh and degraded blood were analyzed as well as blood stored at room temperature, refrigerated, and frozen. Fresh and degraded blood samples produced distinctive VOC patterns with VOC profiles becoming more complex over time. Freezing the blood produced a complex VOC profile that was clearly discriminated from the VOC profile for blood stored at room temperature or in a refrigerator. This study highlights the importance of standardizing the age and storage conditions when using blood as a training aid to ensure cadaver-detection dogs are exposed to an accurate representation of the blood VOCs they may encounter at a scene.

Association between volatile organic compounds and serum neurofilament light chain in US adults.

OBJECTIVE: This study aimed to investigate the associations between exposure to blood volatile organic compounds (VOCs) and the level of serum neurofilament light chain (NfL) in adults. METHODS: We analyzed data from the 2013-2014 National Health and Nutrition Examination Survey (NHANES), including 2008 participants aged 20 to 75 years old. Multiple linear regression models were used to examine the associations between 28 VOCs and NfL after adjusting for multiple potential confounders. Restricted cubic spline (RCS) was used to examine the potential non-linear associations. RESULTS: The linear regression models showed that higher levels of 2,5-dimethylfuran (ß = 0.042, 95 % confidence interval [CI]: 0.001, 0.096), ethyl acetate (ß = 0.118, 95 % CI = 0.008, 0.304), and m-/p-xylene (ß = 0.043, 95%CI = 0.012, 0.074) were associated with higher NfL levels. These estimates were largely consistent after adjusting for multiple confounders. CONCLUSION: The findings of our study suggest a potential association between certain volatile organic compounds (2,5-dimethylfuran, ethyl acetate, and m-/p-xylene) and blood NfL levels, implying that they may have a role in revealing neurodegeneration and influencing neurological health.

The exposure to volatile organic compounds associate positively with overactive bladder risk in U.S. adults: a cross-sectional study of 2007-2020 NHANES.

Objective: The aim of this study was to comprehensively investigate the potential relationship between blood volatile organic compounds (VOCs) and overactive bladder (OAB) risk. Methods: A total of 11,183 participants from the 2007-2020 National Health and Nutrition Examination Survey (NHANES) were included in this cross-sectional study. We used multivariate logistic regression models to investigate the relationship between nine blood VOCs and OAB risk. Restricted cubic spline (RCS) analysis was used to investigate the dose-response relationship between blood VOCs and OAB. In addition, the overall association of blood VOCs with OAB risk was assessed by weighted quantile sum (WQS) regression model. Finally, we conducted subgroup analyses to explore the findings in different high-risk populations. Results: After adjusting for potential confounders, logistic regression analysis revealed that blood 2,5-dimethylfuran (aOR = 2.940, 95% CI: 1.096-7.890, P = 0.032), benzene (aOR = 1.460, 95% CI: 1.044-2.043, P = 0.027) and furan (aOR = 9.426, 95% CI: 1.421-62.500, P = 0.020) were positively independent associated with the risk of OAB. And dose-response risk curves indicated that 2,5-dimethylfuran, benzene and furan in the blood were linearly positive associated with OAB risk. WQS regression analysis showed that exposure to mixed blood VOCs increased the risk of OAB (OR = 1.29, 95% CI: 1.11-1.49), with furans having the greatest weight. In subgroup analyses, we found that OAB was more susceptible to blood VOCs in young and middle-aged, male, non-hypertensive, and alcohol-drinking populations. Conclusions: The results of this study indicate that high exposure to VOCs is independently and positively associated with OAB risk in U.S. adults, particularly 2,5-dimethylfuran, benzene, and furan. In addition, age, gender, hypertension and alcohol consumption may influence the association. Our study provided novel epidemiologic evidence to explore the potential role of environmental pollutants in OAB.

The association between exposure to volatile organic chemicals and serum α-Klotho in USA middle to old aged population: A cross-sectional study from NHANES 2011-2016.

BACKGROUND: Volatile Organic Compounds (VOCs) constitute an omnipresent category of environmental contaminants. Numerous studies have identified associations between various VOCs and human diseases. The anti-aging protein α-Klotho has been shown to exert protective influences across a variety of disease origins and progressions. This study aims to explore the relationship between serum α-Klotho levels and exposure to VOCs in humans. METHODS: This analysis utilized data from 1672 participants aged from 40 to 79 years in 2011-2016 NHANES. Exposure to VOCs was assessed through measurements of urinary VOC metabolites (mVOCs), with 16 mVOCs selected for analysis. Multivariate generalized linear models (GLM), restricted cubic splines (RCS), weighted quantile sum (WQS) regression models, and Bayesian kernel machine regression (BKMR) models were employed to examine the connection between serum α-Klotho and individual mVOCs and mVOCs mixtures, as well as to identify the primary monomeric mVOCs responsible for these associations. RESULTS: Our research revealed that 8 mVOCs exhibited inverse associations with serum α-Klotho levels in GLM and RCS models. Particularly noteworthy, N-Acetyl-S-(2-cyanoethyl)-L-cysteine (CYMA), a metabolite of acrylonitrile, emerged as the most influential mVOC in both WQS and BKMR models. Furthermore, the mVOCs mixture was found to be negatively correlated with serum α-Klotho. The detrimental effects of mVOCs on serum α-Klotho were observed to significantly diminish in individuals with elevated serum vitamin D levels. CONCLUSION: Our study highlights a significant inverse relationship between serum α-Klotho and the mixture of mVOCs, indicating that exposure to VOCs may impact the molecular pathways of aging and related diseases by influencing α-Klotho concentrations. Remarkably, the attenuation of this association by high serum vitamin D levels implies potential therapeutic strategies. Our study underscores the importance of minimizing VOCs exposure to mitigate the adverse effects on α-Klotho. Further research is warranted to elucidate the underlying mechanisms of these relationships.

Biomonitoring of volatile organic compounds and organophosphorus flame retardands in commercial aircrews after "fume and smell events".

Health risks to humans after "fume and smell events", short-term incidents on aircrafts that are accompanied by unpleasant odour or visible smoke, remain a subject of controversy. We assessed exposure to volatile organic compounds (VOC) and organophosphorus compounds (OPC) by biomonitoring in 375 aircrew members after self-reported "fume and smell events" and in 88 persons of the general population. A total of 20 parameters were analysed in blood and urine by gas chromatography and mass spectrometry. Median levels of acetone in blood and urine and 2-propanol in blood were elevated in aircrews compared to controls (p < 0.0001). Additionally, elevated peak exposures, best estimated by the 95th percentiles, were observed in aircrews for n-heptane and n-octane in blood, and acetone, 2,5-hexanedione and o-cresol in urine. Only the maximum observed levels of 2,5-hexandione in urine (768 µg/L) and toluene in blood (77 µg/L) in aircrew members were higher than the current biological exposure indices (BEI® levels) (500 and 20 µg/L, respectively) of the American Conference of Governmental Industrial Hygienists (US-ACGIH) for workers occupationally exposed to n-hexane and toluene, two well-accepted human neurotoxicants. Low-level exposures to n-hexane and toluene could be also observed in controls. The majority of OPC parameters in urine, including those of neurotoxic ortho-isomers of tricresylphosphate, were below the limit of quantitation in both aircrews and controls. Our comparative VOC and OPC analyses in biological samples of a large number of aircrew members and controls suggest that exposures are similar in both groups and generally low.

Blood and breath levels of selected volatile organic compounds in healthy volunteers.

Gas chromatography with mass spectrometric detection (GC-MS) was used to identify and quantify volatile organic compounds in the blood and breath of healthy individuals. Blood and breath volatiles were pre-concentrated using headspace solid phase micro-extraction (HS-SPME) and needle trap devices (NTDs), respectively. The study involved a group of 28 healthy test subjects and resulted in the quantification of a total of 74 compounds in both types of samples. The concentrations of the species under study varied between 0.01 and 6700 nmol L(-1) in blood and between 0.02 and 2500 ppb in exhaled air. Limits of detection (LOD) ranged from 0.01 to 270 nmol L(-1) for blood compounds and from 0.01 to 0.7 ppb for breath species. Relative standard deviations for both measurement regimes varied from 1.5 to 14%. The predominant chemical classes among the compounds quantified were hydrocarbons (24), ketones (10), terpenes (8), heterocyclic compounds (7) and aromatic compounds (7). Twelve analytes were found to be highly present in both blood and exhaled air (with incidence rates higher than 80%) and for 32 species significant differences (Wilcoxon signed-rank test) between room air and exhaled breath were observed. By comparing blood, room air and breath levels in parallel, a tentative classification of volatiles into endogenous and exogenous compounds can be achieved.

GC-MS analysis of ethanol and other volatile compounds in micro-volume blood samples--quantifying neonatal exposure.

A static headspace gas chromatography coupled mass spectrometry (GC-MS) method was developed and fully validated for the quantitative measurement of acetaldehyde, acetone, methanol, ethanol and acetic acid in the headspace of micro-volumes of blood using n-propanol as an internal standard. The linearity of the method was established over the range 0.2-100 mg/L (R(2) > 0.99) and the limits of detection were 0.1-0.2 mg/L and lower limits quantification 0.5-1 mg/L. Precision and accuracies fell within acceptable limits (20 % for LLOQ and 15 %) for both intra- and inter-day analyses for all compounds except acetaldehyde which had inter-day variability of ≤25 %. The method was applied to analyse blood samples from neonatal patients receiving courses of ethanol excipient containing medications. Baseline levels of acetaldehyde, acetone, methanol and ethanol could be measured in patients before dosing commenced and an increase in levels of some volatiles were observed in several neonates after receiving ethanol-containing medications.

Evaluation of matrix effects in the analysis of volatile organic compounds in whole blood with solid-phase microextraction.

The complexity and matrix variability of biological samples requires an accurate evaluation of matrix effects. The dilution of the biological sample is the simplest way to reduce or avoid the matrix effect. In the present study, a set of volatile organic compounds with different volatilities was used to assess the effect of the dilution of blood samples on the extraction efficiency by headspace solid-phase microextraction. It was found that there was a significant matrix effect but that this effect differs significantly depending on the volatility of the compound. A 1:2 (blood/water) dilution was enough to allow quantitative recoveries of those compounds with boiling points <100°C. For compounds with boiling points between 100 and 150°C, the matrix effect was stronger and a 1:5 dilution was required. The dilution of blood samples proved to be inefficient for quantitative recovery of compounds with boiling points >150°C. A 1:5 dilution of the sample allowed detection limits in the range of nanogram per liter to be obtained. This was sufficient to detect the main volatile compounds present in blood and contamination after exposure.