Improved Dynamic Headspace Sampling and Detection using Capillary Microextraction of Volatiles Coupled to Gas Chromatography Mass Spectrometry

Sampling and preconcentration techniques play a critical role in headspace analysis in analytical chemistry. My dissertation presents a novel sampling design, capillary microextraction of volatiles (CMV), that improves the preconcentration of volatiles and semivolatiles in a headspace with high throughput, near quantitative analysis, high recovery and unambiguous identification of compounds when coupled to mass spectrometry. The CMV devices use sol-gel polydimethylsiloxane (PDMS) coated microglass fibers as the sampling/preconcentration sorbent when these fibers are stacked into open-ended capillary tubes. The design allows for dynamic headspace sampling by connecting the device to a hand-held vacuum pump. The inexpensive device can be fitted into a thermal desorption probe for thermal desorption of the extracted volatile compounds into a gas chromatography-mass spectrometer (GC-MS). The performance of the CMV devices was compared with two other existing preconcentration techniques, solid phase microextraction (SPME) and planar solid phase microextraction (PSPME). Compared to SPME fibers, the CMV devices have an improved surface area and phase volume of 5000 times and 80 times, respectively. One (1) minute dynamic CMV air sampling resulted in similar performance as a 30 min static extraction using a SPME fiber. The PSPME devices have been fashioned to easily interface with ion mobility spectrometers (IMS) for explosives or drugs detection. The CMV devices are shown to offer dynamic sampling and can now be coupled to COTS GC-MS instruments. Several compound classes representing explosives have been analyzed with minimum breakthrough even after a 60 min. sampling time. The extracted volatile compounds were retained in the CMV devices when preserved in aluminum foils after sampling. Finally, the CMV sampling device were used for several different headspace profiling applications which involved sampling a shipping facility, six illicit drugs, seven military explosives and eighteen different bacteria strains. Successful detection of the target analytes at ng levels of the target signature volatile compounds in these applications suggests that the CMV devices can provide high throughput qualitative and quantitative analysis with high recovery and unambiguous identification of analytes.

Experimental determination of benzene uptake rate in Tenax TA diffusive samplers

This paper proposes a methodology to predict benzene uptake rate in ambient air, using passive samplers with Tenax TA. Variations in the uptake rate were found to occur as a function of the sampling time; and were greater at the beginning of sampling. An empirical model was obtained and values for uptake rate agree with literature. Concentration prediction errors can be minimized by using sampling times of 4 to 14 days, thus avoiding the influence of excessive uptake rates in the initial days and the influence of back diffusion at the end of the sampling period.

Determination of mitragynine in rat plasma by LC-MS/MS: Application to pharmacokinetics

This study used for the first time LC-MS/MS for the analysis of mitragynine (MIT), a mu-opioid agonist with antinociceptive and antitussive properties, in rat plasma. Mitragynine and the internal standard (amitriptyline) were extracted from plasma with hexane-isoamyl alcohol and resolved on a Lichrospher (R) RP-SelectB column (9.80 and 12.90 min, respectively). The quantification limit was 0.2 ng/mL within a linear range of 0.2-1000 ng/mL The method was applied to quantify mitragynine in plasma samples of rats (n = 8 per sampling time) treated with a single oral dose of 20 mg/kg. The following pharmacokinetic parameters were obtained (mean): maximum plasma concentration: 424 ng/mL; time to reach maximum plasma concentration: 1.26 h; elimination half-life: 3.85 h, apparent total clearance: 6.35 L/h/kg, and apparent volume of distribution: 37.90 L/kg. (C) 2009 Elsevier B.V. All rights reserved.

Population pharmacokinetics of perhexiline from very sparse, routine monitoring data

Using NONMEM, the population pharmacokinetics of perhexiline were studied in 88 patients (34 F, 54 M) who were being treated for refractory angina. Their mean +/- SD (range) age was 75 +/- 9.9 years (46-92), and the length of perhexiline treatment was 56 +/- 77 weeks (0.3-416). The sampling time after a dose was 14.1 +/- 21.4 hours (0.5-200), and the perhexiline plasma concentrations were 0.39 +/- 0.32 mg/L (0.03-1.56). A one-compartment model with first-order absorption was fitted to the data using the first-order (FO) approximation. The best model contained 2 subpopulations (obtained via the $MIXTURE subroutine) of 77 subjects (subgroup A) and 11 subjects (subgroup B) that had typical values for clearance (CL/F) of 21.8 L/h and 2.06 L/h, respectively. The volumes of distribution (V/F) were 1470 L and 260 L, respectively, which suggested a reduction in presystemic metabolism in subgroup B. The interindividual variability (CV%) was modeled logarithmically and for CL/F ranged from 69.1% (subgroup A) to 86.3% (subgroup B). The interindividual variability in V/F was 111%. The residual variability unexplained by the population model was 28.2%. These results confirm and extend the existing pharmacokinetic data on perhexiline, especially the bimodal distribution of CL/F manifested via an inherited deficiency in hepatic and extrahepatic CYP2D6 activity.

Impact of maritime air mass trajectories on the Western European coast urban aerosol

Lisbon is the largest urban area in the Western European coast. Due to this geographical position the Atlantic Ocean serves as an important source of particles and plays an important role in many atmospheric processes. The main objectives of this study were to (1) perform a chemical characterization of particulate matter (PM2.5) sampled in Lisbon, (2) identify the main sources of particles, (3) determine PM contribution to this urban area, and (4) assess the impact of maritime air mass trajectories on concentration and composition of respirable PM sampled in Lisbon. During 2007, PM2.5 was collected on a daily basis in the center of Lisbon with a Partisol sampler. The exposed Teflon filters were measured by gravimetry and cut into two parts: one for analysis by instrumental neutron activation analysis (INAA) and the other by ion chromatography (IC). Principal component analysis (PCA) and multilinear regression analysis (MLRA) were used to identify possible sources of PM2.5 and determine mass contribution. Five main groups of sources were identified: secondary aerosols, traffic, calcium, soil, and sea. Four-day backtracking trajectories ending in Lisbon at the starting sampling time were calculated using the HYSPLIT model. Results showed that maritime transport scenarios were frequent. These episodes were characterized by a significant decrease of anthropogenic aerosol concentrations and exerted a significant role on air quality in this urban area.

Strategies for the development of tdm for targeted anticancer agents

Most of the novel targeted anticancer agents share classical characteristics that define drugs as candidates for blood concentration monitoring: long-term therapy; high interindividual but restricted intraindividual variability; significant drug-drug and drug- food interactions; correlations between concentration and efficacy/ toxicity with rather narrow therapeutic index; reversibility of effects; and absence of early markers of response. Surprisingly though, therapeutic concentration monitoring has received little attention for these drugs despite reiterated suggestions from clinical pharmacologists. Several issues explain the lack of clinical research and development in this field: global tradition of empiricism regarding treatment monitoring, lack of formal conceptual framework, ethical difficulties in the elaboration of controlled clinical trials, disregard from both drug manufacturers and public funders, limited encouragement from regulatory authorities, and practical hurdles making dosage adjustment based on concentration monitoring a difficult task for prescribers. However, new technologies are soon to help us overcome these obstacles, with the advent of miniaturized measurement devices able to quantify circulating drug concentrations at the point-of-care, to evaluate their plausibility given actual dosage and sampling time, to determine their appropriateness with reference to therapeutic targets, and to advise on suitable dosage adjustment. Such evolutions could bring conceptual changes into the clinical development of drugs such as anticancer agents, while increasing the therapeutic impact of population PK-PD studies and systematic reviews. Research efforts in that direction from the clinical pharmacology community will be essential for patients to receive the greatest benefits and the least harm from new anticancer treatments. The example of imatinib, the first commercialized tyrosine kinase inhibitor, will be outlined to illustrate a potential research agenda for the rational development of therapeutic concentration monitoring.

First nationwide study on driving under the influence of drugs in Switzerland.

In Switzerland, a two-tier system based on impairment by any psychoactive substances which affect the capacity to drive safely and zero tolerance for certain illicit drugs came into force on 1 January 2005. According to the new legislation, the offender is sanctioned if Delta(9)-tetrahydrocannabinol THC is >or=1.5ng/ml or amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyethylamphetamine (MDEA), cocaine, free morphine are >or=15ng/ml in whole blood (confidence interval+/-30%). For all other psychoactive substances, impairment must be proven in applying the so-called "three pillars expertise". At the same time the legal blood alcohol concentration (BAC) limit for driving was lowered from 0.80 to 0.50g/kg. The purpose of this study was to analyze the prevalence of drugs in the first year after the introduction of the revision of the Swiss Traffic Law in the population of drivers suspected of driving under the influence of drugs (DUID). A database was developed to collect the data from all DUID cases submitted by the police or the Justice to the eight Swiss authorized laboratories between January and December 2005. Data collected were anonymous and included the age, gender, date and time of the event, the type of vehicle, the circumstances, the sampling time and the results of all the performed toxicological analyses. The focus was explicitly on DUID; cases of drivers who were suspected to be under the influence of ethanol only were not considered. The final study population included 4794 DUID offenders (4243 males, 543 females). The mean age of all drivers was 31+/-12 years (range 14-92 years). One or more psychoactive drugs were detected in 89% of all analyzed blood samples. In 11% (N=530) of the samples, neither alcohol nor drugs were present. The most frequently encountered drugs in whole blood were cannabinoids (48% of total number of cases), ethanol (35%), cocaine (25%), opiates (10%), amphetamines (7%), benzodiazepines (6%) and methadone (5%). Other medicinal drugs such as antidepressants and benzodiazepine-like were detected less frequently. Poly-drug use was prevalent but it may be underestimated because the laboratories do not always analyze all drugs in a blood sample. This first Swiss study points out that DUID is a serious problem on the roads in Switzerland. Further investigations will show if this situation has changed in the following years.

Aggregate stability as affected by short and long-term tillage systems and nutrient sources of a hapludox in southern Brazil

The ability of a soil to keep its structure under the erosive action of water is usually high in natural conditions and decreases under frequent and intensive cultivation. The effect of five tillage systems (NT = no-till; CP = chisel plowing and one secondary disking; CT = primary and two secondary distings; CTb = CT with crop residue burning; and CTr = CT with removal of crop residues from the field), combined with five nutrient sources (C = control, no nutrient application; MF = mineral fertilizers according to technical recommendations for each crop; PL = 5 Mg ha-1 y-1 fresh matter of poultry litter; CM = 60 m³ ha-1 y-1 slurry cattle manure; and SM = 40 m³ ha-1 y-1 slurry swine manure) on wet-aggregate stability was determined after nine years (four sampled soil layers) and on five sampling dates in the 10th year (two sampled soil layers) of the experiment. The size distribution of the air-dried aggregates was strongly affected by soil bulk density, and greater values of geometric mean diameter (GMD AD) found in some soil tillage or layer may be partly due to the higher compaction degree. After nine years, the GMD AD on the surface was greater in NT and CP compared to conventional tillage systems (CT, CTb and CTr), due to the higher organic matter content, as well as less soil mobilization. Aggregate stability in water, on the other hand, was affected by the low variation in previous gravimetric moisture of aggregates, which contributed to a high coefficient of variation of this attribute. The geometric mean diameter of water-stable aggregates (GMD WS) was highest in the 0.00-0.05 m layer in the NT system, in the layers 0.05-0.10 and 0.12-0.17 m in the CT, and values were intermediate in CP. The stability index (SI) in the surface layers was greater in treatments where crop residues were kept in the field (NT, CP and CT), which is associated with soil organic matter content. No differences were found in the layer 0.27-0.32 m. The effect of nutrient sources on GMD AD and GMD WS was small and did not affect SI.

Emission of nitrous oxide and carbon dioxide from semi-arid tropical soils in Chiapas México

The semi-arid region of Chiapas is dominated by N2 -fixing shrubs, e.g., Acacia angustissima. Urea-fertilized soil samples under maize were collected from areas covered and uncovered by A. angustissima in different seasons and N2O and CO2 emissions were monitored. The objective of this study was to determine the effects of urea and of the rainy and dry season on gas emissions from semi-arid soil under laboratory conditions. Urea and soil use had no effect on CO2 production. Nitrons oxide emission from soil was three times higher in the dry than in the rainy season, while urea fertilization doubled emissions. Emissions were twice as high from soil sampled under A. angustissima canopy than from arable land, but 1.2 lower than from soil sampled outside the canopy, and five times higher from soil incubated at 40 % of the water-holding capacity (WHC) than at soil moisture content, but 15 times lower than from soil incubated at 100 WHC. It was found that the soil sampling time and water content had a significant effect on N2O emissions, while N fertilizer and sampling location were less influent.

Influence of mineral fertilization on edaphic fauna in Acacia auriculiformis (A. Cunn) plantations

Fertilization and/or the accumulation of organic matter from plant residues can influence the composition of soil and litter community. The goal of this study was to evaluate the effects of P and K fertilization on total faunal and nematode faunal composition and richness in plant litter and soil for 360 days in an area reforested with Acacia auriculiformis (A. Cunn), located in the municipality of Conceição de Macabu in the State of Rio de Janeiro. For each treatment (fertilized and unfertilized plots), samples of litter and soil (to a depth of 5 cm) were collected and transferred into a Berlese-Tüllgren funnels for the extraction of fauna. Mesofauna and macrofauna were quantified, and the major taxa identified. Nematodes were extracted by centrifugal flotation in sucrose solution and identified according to feeding habits. Density (number of individuals m-2) of total fauna, microphages, social insects and saprophages varied significantly per treatment and sampling time in both litter and soil. The total number of individuals collected was 5,127, and the total number of nematodes 894. Phosphorus and potassium fertilization resulted in an increase in total fauna density and richness in the litter due to an increased abundance of social insects, saprophages and herbivores. In the soil, fertilization increased the saprophage and predator densities. Saprophages were the predominant taxa in the litter, while social insects (Formicidae) prevailed in the soil. Litter nematode populations were favored by mineral fertilization. Bacteriophages were the predominant nematode group in both litter and soil.

Comparison of hospital-wide and unit-specific cumulative antibiograms in hospital- and community-acquired infection.

BACKGROUND: Empirical antibacterial therapy in hospitals is usually guided by local epidemiologic features reflected by institutional cumulative antibiograms. We investigated additional information inferred by aggregating cumulative antibiograms by type of unit or according to the place of acquisition (i.e. community vs. hospital) of the bacteria. MATERIALS AND METHODS: Antimicrobial susceptibility rates of selected pathogens were collected over a 4-year period in an university-affiliated hospital. Hospital-wide antibiograms were compared with those selected by type of unit and sampling time (<48 or >48 h after hospital admission). RESULTS: Strains isolated >48 h after admission were less susceptible than those presumably arising from the community (<48 h). The comparison of units revealed significant differences among strains isolated >48 h after admission. When compared to hospital-wide antibiograms, susceptibility rates were lower in the ICU and surgical units for Escherichia coli to amoxicillin-clavulanate, enterococci to penicillin, and Pseudomonas aeruginosa to anti-pseudomonal beta-lactams, and in medical units for Staphylococcus aureus to oxacillin. In contrast, few differences were observed among strains isolated within 48 h of admission. CONCLUSIONS: Hospital-wide antibiograms reflect the susceptibility pattern for a specific unit with respect to community-acquired, but not to hospital-acquired strains. Antibiograms adjusted to these parameters may be useful in guiding the choice of empirical antibacterial therapy.

A low-cost trap for Cerambycidae monitoring in forest plantations in Brazil

The objective of this work was to evaluate the use of a low-cost trap to capture Cerambycidae in different seasons in planted forests in Brazil. Thirty polyethylene-terephthalate trap bottles per hectare were used, disposed at every 50 m. The traps were red painted and contained glass flasks with a mixture of ethanol, methanol and benzaldehyde. There were soap and water at the trap bottom. The traps were checked biweekly for beetle presence. Sampling time required one minute per sample, and traps were easy to use. Total sampling cost, including materials and labor, was US$ 13.46 per sample. Six Cerambycidae species were captured along the dry and rainy seasons.

Gota suspensa para avaliação de aldeído total no ar interno e externo do ambiente

A sensitive and simple system was proposed for the in situ measurement of total aldehyde in outdoor or indoor ambient. The method is based on the use of a reagent drop as an useful interface to preconcentrate the sample prior to determination of total aldehyde as formaldehyde. The drop is formed at the tip of a cylindrical tube that contains two optical fibers placed on opposite sides and in contact with the reagent solution. One optical fiber carries the red light to the drop form a light emitting diode (LED). The transmitted light is measured by a second optical fiber/photodiode system. The analytical signal is read and converted into absorbance. The reagent solution of 3-methyl-2-benzothiazoline hydrazone (MBTH) forms a blue cation during reaction with formaldehyde that can be measured at 660 nm. Some aspects of kinetics reaction formation of dye were reevaluated. The formaldehyde reacts with MBTH and forms the azine in about 12 min. The oxidation of MBTH by Fe (III) and the formation of dye requires 3 min. The absorbance of the reagent drop is proportional to the sampling time and to the analyte concentration. The absorbance signal increases with increased sample gas flow until a maximum is reached then decreases until it forms a plateau. The proposed method was evaluated using both outdoor and indoor samples, and it was shown to viable provide an accurate measure of total aldehyde.

Uso de agrotóxicos em cana-de-açúcar na bacia do Rio Corumbataí e o risco de poluição hídrica

The state of São Paulo is the main Brazilian consumer of pesticides. Sugar cane, which uses a great amount of these products, is extensivelly cultivated in this state, such as in the Corumbataí river basin, an important source of water for the region. In order to implement an efficient and low-cost monitoring program, the temporal characterization of the use of pesticides on sugar cane in this basin was performed. After knowing the seasonal trends of consumption, a better choice of sampling time, became possible. The combination of data from this survey with partitioning indices, average doses and toxicological classifications showed to be important for defining the pesticides to be included in the monitoring program.

Experimental determination of benzene uptake rate in Tenax TA diffusive samplers

This paper proposes a methodology to predict benzene uptake rate in ambient air, using passive samplers with Tenax TA. Variations in the uptake rate were found to occur as a function of the sampling time; and were greater at the beginning of sampling. An empirical model was obtained and values for uptake rate agree with literature. Concentration prediction errors can be minimized by using sampling times of 4 to 14 days, thus avoiding the influence of excessive uptake rates in the initial days and the influence of back diffusion at the end of the sampling period.