Fast determination of Z-ligustilide in plasma by gas chromatography/mass spectrometry following headspace single-drop microextraction

Angelica sinensis (danggui in Chinese) is a common traditional Chinese medicine (TCM), and its essential oil has been used for the treatment of many diseases such as hepatic fibrosis. Z-Ligustilide has been found to be an important active component in the TCM essential oil. In this work, for the first time, headspace single-drop microextraction (HS-SDME) followed by gas chromatography-mass spectrometry (GC-MS) was developed for the determination of Z-ligustilide in rabbit plasma after oral administration of essential oil of danggui. The extraction parameters of solvent selection, solvent volume, sample temperature, extraction time, stirring rate, and ion strength were systemically optimized. Furthermore, the method linearity, detection limit, and precision were also investigated. It was shown that the proposed method provided good linearity (0.02-20 microg/mL, R2 = 0.997), low detection limit (10 ng/mL), and good precision (RSD value less than 9%). Finally, HS-SDME followed by GC/MS was used for fast determination of Z-ligustilide in rabbit plasma at different time intervals after oral administration of danggui essential oil. The experimental results suggest that HS-SDME followed by GC/MS is a simple, sensitive, and low-cost method for the determination of Z-ligustilide in plasma, and a low-cost approach to pharmacokinetics studies of active components in TCMs.     

Development of water-phase derivatization followed by solid-phase microextraction and gas chromatography/mass spectrometry for fast determination of valproic acid in human plasma

In this study, a simple, rapid, and sensitive method was developed and validated for the quantification of valproic acid (VPA), an antiepileptic drug, in human plasma, which was based on water-phase derivatization followed by headspace solid-phase microextraction (HS-SPME) and gas chromatography/mass spectrometry (GC/MS). In the proposed method, VPA in plasma was rapidly derivatized with a mixture of isobutyl chloroformate, ethanol and pyridine under mild conditions (room temperature, aqueous medium), and the VPA ethyl ester formed was headspace-extracted and simultaneously concentrated using the SPME technique. Finally, the analyte extracted on SPME fiber was analyzed by GC/MS. The experimental parameters and method validations were studied. The optimal conditions were obtained: PDMS fiber, stirring rate of 1100 rpm, sample temperature of 80 degrees C, extraction time of 20 min, NaCl concentration of 30%. The proposed method had a limit of quantification (0.3 microg/mL), good recovery (89-97%) and precision (RSD value less than 10%). Because the proposed method combined a rapid water-phase derivatization with a fast, simple and solvent-free sample extraction and concentration technique of SPME, the sample preparation time was less than 25 min. This much shortens the whole analysis time of VPA in plasma. The validated method has been successfully used to analyze VPA in human plasma samples for application in pharmacokinetic studies. All these results show that water-phase derivatization followed by HS-SPME and GC/MS is an alternative and powerful method for fast determination of VPA in biological fluids.     

Determination of diisopropylfluorophosphate in rat plasma and brain tissue by headspace solid-phase microextraction gas chromatography/mass spectrometry

A simple, sensitive and rapid method for the determination of diisopropylfluorophosphate (DFP) in rat plasma and brain tissue using headspace solid-phase microextraction (HS-SPME) and gas chromatography/mass spectrometry (GC/MS) is presented. A 65 microm polydimethylsiloxane/divinylbenzene (PDMS/DVB) fiber was selected for sampling. The main parameters affecting the SPME process such as extraction and desorption temperature, extraction and desorption time, salt addition, and fiber preheating time were optimized in each matrix to enhance the extraction efficiency of the method. The lower limits of quantitation for DFP in plasma and brain tissue were 1 ng/mL and 3 ng/g, respectively. The method showed good linearity over the range from 1-100 ng/mL in plasma and 3-300 ng/g in brain tissue with correlation coefficient (R(2)) values higher than 0.995. The precision and accuracy for intra-day and inter-day were less than 10%. The relative recoveries in plasma and brain for DFP were greater than 50%. Stability tests including autosampler and freeze and thaw were also investigated. This validated method was successfully applied to study the neurobehavioral effects of low-level organophosphate exposures. Copyright (c) 2008 John Wiley & Sons, Ltd.     

Trace level determination of trichloroethylene in biological samples by headspace solid-phase microextraction gas chromatography/negative chemical ionization mass spectrometry

A gas chromatography/negative chemical ionization mass spectrometry (GC/NCIMS) method using headspace solid-phase microextraction (HS-SPME) was developed for the determination of trichloroethylene (TCE) in blood, liver, kidney, lung and brain. The method was optimized with respect to several parameters including extraction time, extraction temperature, desorption time and salt addition. The method showed good linearity over the range of 0.025-25 ng/mL in blood and 0.075-75 ng/g in tissues with correlation coefficient (R2) values higher than 0.99. The precision and accuracy for intra-day and inter-day measurements were less than 10%. The relative recoveries of all matrices were greater than 52%. Samples showed no significant loss during 8 h in the autosampler and following three freeze/thaw cycles. Validation results demonstrated that selected-ion monitoring of the 35Cl and 37Cl isotopes using NCI resulted in reliable and sensitive quantitation. This validated method was successfully applied to study the toxicokinetics of TCE following oral administration of extremely low doses of this potential human carcinogen to small test animals (rats).     

Volatile fingerprints of artemisinin-rich Artemisia annua cultivars by headspace solid-phase microextraction gas chromatography/ mass spectrometry

The cultivar Anamed (A3) is a hybrid of Artemisia annua with a high content of the secondary metabolite artemisinin, a well-known antimalarial drug. Here we report for the first time the volatile profile of fresh leaves of this hybrid in comparison with that of Artemisia annua L. wild-type species. Evaluation and comparison of the volatile profiles of A. annua genotypes with different content in artemisinin were carried out by headspace solid-phase microextraction (HS-SPME) coupled with gas chromatography/mass spectrometry (GC/MS) that was performed on fresh leaves of the plants under investigation using a polydimethylsiloxane (PDMS) fiber. The chromatograms obtained from hybrids with a high content of artemisinin (A. annua cv. Anamed A3 and A. annua cv. Artemis F2) reveal the total absence of artemisia ketone, one of the major and characteristic compounds of the wild-type A. annua L., along with a significantly lower variety of volatile compounds. In conclusion, HS-SPME coupled with GC/MS is a very useful, non-destructive and efficient method to describe the volatile pattern of Artemisia annua cultivars. It represents a rapid screening method for the evaluation of volatile biomarkers like artemisia ketone, whose absence is typical of artemisinin-rich A. annua cultivars.     

Detection of perfluorocarbons in blood by headspace solid-phase microextraction combined with gas chromatography/mass spectrometry.

A new method of detection of perfluorocarbon molecules (PFCs) in blood sample has been established. After an extraction and pre-concentration step performed by headspace solid-phase microextraction (HS-SPME), the PFCs are detected by gas chromatography-mass spectrometry (GC/MS) with an ion trap mass spectrometer in MS and MS/MS modes. The influence of different parameters on the SPME process is discussed. The limit of detection and the linearity of the procedure have been determined for two PFCs.     

Optimization, validation and application of a method for the determination of trichloroethylene in rat plasma by headspace solid-phase microextraction gas chromatography mass spectrometry

Trichloroethylene (TCE) is a small halogenated compound that has been used extensively as a metal degreaser and a solvent for the past 100 years. As a result of its widespread use, TCE can be found in the groundwater of about one-third of the hazardous waste sites on the United States Environmental Protection Agency's National Priorities List. Human exposure to TCE in the environmental media is of concern because TCE has been found to be carcinogenic in laboratory animals. This paper describes the development and validation of a HS-SPME-GC/MS method for determination of TCE in rat plasma. The effects of different parameters such as sample volume, extraction and desorption conditions, fiber positions and salt addition were investigated and optimized. The method is rapid, simple, sensitive and requires a very small sample volume. The lower limit of quantitation was 0.25 ng/mL and correlation coefficient (r(2)) values for the linear range of 0.25-100 ng/mL were 0.996 or greater. The precision and accuracy for intra-day and inter-day were better than 8.0%. This validated method was successfully applied to study the toxicokinetic behavior of TCE following low levels of oral administration. Copyright (c) 2008 John Wiley & Sons, Ltd.     

Fast determination of paeonol in plasma by headspace solid-phase microextraction followed by gas chromatography-mass spectrometry

Paeonol is the active component in the traditional Chinese medicines (TCMs), such as Cynanchum paniculatum, which has been used to treat many diseases, such as eczema. In this work, a simple, rapid and sensitive method was developed for the determination of paeonol in rabbit plasma, which was based on headspace solid-phase microextraction (HS-SPME) followed by gas chromatography-mass spectrometry (GC-MS). The extraction parameters of fiber coating, sample temperature, extraction time, stirring rate and ion strength were systemically optimized; the method linearity, detection limit and precision were also investigated. It was shown that the proposed method provided a good linearity (0.02-20 μg mL⁻¹, R² > 0.990), low detection limit (2.0 ng mL⁻¹) and good precision (R.S.D. value less than 8%). Finally, GC/MS following HS-SPME was applied to fast determination of paeonol in rabbit plasma at different time point after oral demonstration of Cynanchum paniculatum essential oil. The experimental results suggest that the proposed method provided an alternative and novel approach to the pharmacokinetics study of paeonol in the TCMs.     

Determination of phthalates and adipate in bottled water by headspace solid-phase microextraction and gas chromatography/mass spectrometry

The performance of three fibres for the headspace solid-phase microextraction (SPME) of di-2-ethylhexyl adipate (DEHA) and eight phthalates in water was investigated systematically under different extraction conditions. Good responses on the 65 microm polydimethylsiloxane/divinylbenzene (PDMS/DVB) SPME fibre were observed for DEHA and all phthalates. The polydimethylsiloxane (PDMS) SPME fibre had very poor responses for the lighter and slightly polar phthalates, dimethyl phthalate (DMP) and diethyl phthalate (DEP), while the divinylbenzene/carboxen/polydimethylsiloxane (DVB/CAR/PDMS) SPME fibre had very poor responses for the heavier and non-polar adipate and phthalates. The salt (NaCl) was found to increase the partitioning of DMP, DEP, diisobutyl phthalate (DiBP), di-n-butyl phthalate, and benzyl butyl phthalate (BBP) from water into the headspace, while partitioning of heavier adipate and phthalates from water into headspace was suppressed when the concentration of NaCl was above 10%. The automated headspace SPME methods were developed and validated under two different salting conditions (30% NaCl for DMP, DEP and BBP, and 10% for DEHA, DiBP, DBP, di-n-hexyl phthalate (DHP), di-2-ethylhexyl phthalate (DEHP), and di-n-octyl phthalate (DOP)). Linearity with R(2) values better than 0.9949 was observed for DEHA and eight phthalates over the range from 0.1 to 20 microg L(-1). Method detection limits ranged from 0.003 microg L(-1) for DOP to 0.085 microg L(-1) for BBP. Good repeatability was observed for DEHA and most phthalates with relative standard deviation (RSD) values less than 10%. The methods were used to analyse bottled water samples for DEHA and eight phthalates. DMP, DHP, BBP, DEHA and DOP were not detected in any samples. Concentrations of the other phthalates were low (around sub-ppb) except for DBP in the water from a polycarbonate bottle at 1.72 microg L(-1).     

Application of gas chromatography coupled to chemical ionisation mass spectrometry following headspace solid-phase microextraction for the determination of free volatile fatty acids in aqueous samples

Gas chromatography coupled to positive and negative ion chemical ionisation mass spectrometry was evaluated for the determination of free volatile fatty acids (VFAs) from aqueous samples by headspace solid-phase microextraction. Negative ion chemical ionisation in the selected ion monitoring mode using ammonia as reagent gas provided acceptable sensitivity and the highest selectivity for the determination of C2-C7 fatty acids using a polydimethylsiloxane-Carboxen fibre. Detection limits in the range of 150 microg l(-1) for acetic acid and from 2 to 6 microg l(-1) for the remaining carboxylic acids were achieved. The reproducibility of the method was between 9 and 16%. The developed analytical procedure was applied to the analysis of VFAs in raw sewage. The absence of interfering peaks provided a more accurate determination of acetic, propionic, butyric and isovaleric acids than a similar analytical scheme but using a flame ionisation detector.     

Determination of midazolam in human plasma by solid-phase microextraction and gas chromatography/mass spectrometry.

A new method is described for the qualitative and quantitative analysis of midazolam, a short-acting 1,4-imidazole benzodiazepine, in human plasma. It involves a plasma deproteinization step, solid-phase microextraction (SPME) of midazolam using an 85-microm polyacrylate fiber, and its detection by gas chromatography/mass spectrometry (GC/MS) in selected ion monitoring (SIM) mode, using pinazepam as internal standard. The assay is linear over a midazolam plasma range of 1.5-300 ng/mL, relative intra- and inter-assay standard deviations at 5 ng/mL are below 7%, and the limit of detection is 1 ng/mL. The method is simple, fast and sufficiently sensitive to be applied in clinical and forensic toxicology as well as for purposes of therapeutic drug monitoring.     

An improved method for cyanide determination in blood using solid-phase microextraction and gas chromatography/mass spectrometry

A new method is described for the qualitative and quantitative analysis of cyanide, a very short-acting and powerful toxic agent, in human whole blood. It involves the conversion of cyanide into hydrogen cyanide and its subsequent headspace solid-phase microextraction (HS-SPME) and detection by gas chromatography/mass spectrometry (GC/MS) in selected ion monitoring (SIM) mode. Optimizing the conditions for the GC/MS (type of column, injection conditions, temperature program) and SPME (choice of SPME fiber, effect of salts, adsorption and desorption times, adsorption temperature) led to the choice of a 75-microm carboxen/polydimethylsiloxane SPME fiber, with D3-acetonitrile as internal standard, and a capillary GC column with a polar stationary phase. Method validation was carried out in terms of linearity, precision and accuracy in both aqueous solutions and blood. The limit of detection (LOD) and limit of quantitation (LOQ) were determined only in aqueous solutions. The assay is linear over three orders of magnitude (water 0.01-10, blood 0.05-10 microg/mL); and the LOD and LOQ in water were 0.006 and 0.01 microg/mL, respectively. Good intra- and inter-assay precision was obtained, always <8%. The method is simple, fast and sensitive enough for the rapid diagnosis of cyanide intoxication in clinical and forensic toxicology.     

Rapid gas chromatography/mass spectrometry quinine determination in plasma after automated solid-phase extraction

The combined use of an automatic solid-phase extraction (SPE) apparatus with Oasis MCX cartridges and gas chromatography/mass spectrometry (GC/MS) to rapidly quantify quinine in biological samples with cyproheptadine as the internal standard is described. The selected ion monitoring mode, with the quantification ions m/z 136 and 287 (qualifier ions: m/z 261, 381 and 215, 96), allows the estimation of quinine levels, respectively. Separation was completed within 12.7 min. Excellent linearity was found up to 10 000 microg/L of plasma. The limit of detection (LOD) was 12.2 microg/L and the limit of quantification (LOQ) was 40.6 microg/L. High reproducibility (intra-assay CV range 1.9-4.3%, inter-assay CV range 2.2-11.3%) and accuracy values (intra-assay range 83.2-103.7%, inter-assay range 86.8-103.7%) were obtained. Recoveries were concentration-independent (97.2% and 89.8% for 4000 and 10 000 microg/L, respectively). This sensitive, simple assay for quinine in various matrices meets the current requirements for bioanalytical assays and may be used to monitor quinine levels in patients developing severe malaria with acute renal failure during hemofiltration. The optimal quinine dose in this situation is not really established and to improve clinical care, quinine concentrations might be explored to improve efficacy and minimise potential toxicity.     

Optimisation of wort volatile analysis by headspace solid-phase microextraction in combination with gas chromatography and mass spectrometry

The aim of this study was to create a simple, solventless technique without derivatisation in order to analyze a broad range of volatiles in beer wort. A method was developed using headspace solid-phase microextraction coupled with gas chromatography and mass spectrometry. The procedure was optimised by selection of the appropriate fibre and optimisation of extraction temperature, extraction time, and salting-out. The detection limits were well below the actual wort concentrations of the selected volatiles, ranging from 12 ng/l for linalool to 0.53 microg/l for furfural. Moreover, the procedure showed a good linearity and was applied to the analysis of wort samples taken from a wort boiling process in an industrial brewery.     

Simultaneous determination of volatile and semi-volatile aromatic hydrocarbons in virgin olive oil by headspace solid-phase microextraction coupled to gas chromatography/mass spectrometry

A reliable, simple and relatively fast method for the simultaneous determination of volatile and semi-volatile aromatic hydrocarbons in virgin olive oil was developed, based on headspace solid-phase microextraction (HS-SPME). The investigation regarded eco-contaminants such as alkylated monoaromatic hydrocarbons from C1- to C4-benzenes and light polyaromatic hydrocarbons up to four aromatic rings. Sampling and chromatographic conditions were optimized by using standard solutions in deodorized olive oil and the analytical performances of the method were determined. The proposed method was then applied to real samples of virgin olive oil were the target hydrocarbons could be identified and quantified. Several of them had not been previously quantified in virgin olive oil. Moreover, by the analysis of olive oil samples an additional number of C4-benzenes could be tentatively identified.     

Monoterpene and sesquiterpene hydrocarbons of virgin olive oil by headspace solid-phase microextraction coupled to gas chromatography/mass spectrometry

In the present article, a headspace solid-phase microextraction method coupled to GC/MS was developed and applied for the simultaneous determination of mono- and sesquiterpenic hydrocarbons in virgin olive oils of different olive variety and geographical origin. Analysis of various oils resulted in the simultaneous detection of 15 monoterpenes and 30 sesquiterpenes. Some of these hydrocarbons were previously reported to be constituents of virgin olive oil terpenoid fraction, although we also detected some terpenic hydrocarbons that have not previously been documented as present in virgin olive oil. Significant differences were detected in the proportion of terpenic compounds in oils obtained from different olive varieties grown in different geographical areas. The monoterpene, and particularly the sesquiterpene composition of olive oil may be used to distinguish samples from different cultivar and geographical areas.     

Automated determination of ethyl carbamate in stone-fruit spirits using headspace solid-phase microextraction and gas chromatography-tandem mass spectrometry

A fully automated procedure using headspace solid-phase microextraction (HS-SPME) followed by gas chromatographic/tandem mass spectrometric (GC/MS/MS) detection was developed for the determination of the toxic contaminant ethyl carbamate (EC) in stone-fruit spirits. After addition of deuterated internal standard, the optimised HS-SPME extraction with carbowax/divinylbenzene fibres (30 min at 70 degrees C) was done applying salting out with sodium chloride in the presence of pH 7 buffer solution. For quantitative analysis the characteristic fragmentations of m/z 74>44 and m/z 62>44 for ethyl carbamate as well as m/z 64>44 for ethyl carbamate-d5 were monitored in the multiple reaction monitoring (MRM) mode using a triple quadrupole instrument. In the validation studies, ethyl carbamate exhibited good linearity with a regression coefficient of 0.998. The limits of detection and quantitation were 0.03 and 0.11 mg/l. The precision never exceeded 4.3% (intraday) and 8.2% (interday) at any of the concentrations examined. A good agreement of analysis results in comparison to conventional sample clean-up over diatomaceous earth columns was found (R = 0.956, Bias = 0.08 mg/l). The new HS-SPME/GC/MS/MS procedure is suitable for the fast, reliable and inexpensive determination of ethyl carbamate in alcoholic beverages in an automated, and therefore, convenient procedure.     

Determination of bisphenol A in water by isotope dilution headspace solid-phase microextraction and gas chromatography/mass spectrometry without derivatization

The original solid-phase microextraction (SPME) fibers use an epoxy resin adhesive that releases bisphenol A (BPA) during thermal desorption of the fiber. This adversely affects the method detection limit and accuracy when these products are used for the determination of BPA. In this work, 5 new metal alloy SPME fibers that do not use epoxy resins were compared for the extraction of BPA in water. The performance of the optimum SPME fiber with 60 microm carbowax-polyethylene glycol coating for the headspace SPME of BPA in water was investigated systematically under different extraction conditions. Salt was found to increase the partitioning of BPA from water into the headspace until saturation was reached. Partitioning of BPA from water into the headspace also increased at higher extraction temperatures, as did longer extraction times. However, extraction of BPA from water onto the SPME fiber was not improved for solutions adjusted to pH 2 compared to the unadjusted neutral solutions. The new BPA method showed good linearity over the concentration range of 2.5 to 40 microg/L [correlation coefficient (r2) = 0.995] .The method detection limit for BPA was 0.5 microg/L, while the instrument detection limit was as low as 0.05 microg/L. Good repeatability was observed for BPA at levels of 5 and 20 microg/L with relative standard deviation values < 10%. The automated headspace SPME method developed in this work was used to investigate migration of BPA from polycarbonate bottles into water, and levels of BPA in water ranged from 1.7 to 4.1 microg/L.     

Rapid white truffle headspace analysis by proton transfer reaction mass spectrometry and comparison with solid-phase microextraction coupled with gas chromatography/mass spectrometry

The gastronomic relevance and high price of white truffle are related mainly to its unique aroma. Here we evaluate, for the first time, the possibility of characterizing in a rapid and non-destructive way the aroma of white truffles based on proton transfer reaction mass spectrometry (PTR-MS). We indicate that anonymous PTR-MS fingerprinting allows sample classification and we also compare qualitatively and quantitatively PTR-MS data with measurements made by solid-phase microextraction gas chromatography (SPME-GC) of the same samples under the same conditions. PTR-MS fragmentation data of truffle-relevant compounds are also published here for the first time. Most of the sulfur-containing compounds detected by GC and relevant for white truffle aroma have a high positive correlation with single PTR-MS peaks. Our work indicates that, after preliminary comparison with GC data, PTR-MS is a new tool for the rapid, quantitative and non-invasive characterization of white truffle by direct headspace injection without any pre-concentration.     

Rapid monitoring of sulfur mustard degradation in solution by headspace solid-phase microextraction sampling and gas chromatography mass spectrometry

A method using headspace solid-phase microextraction (HS-SPME) followed by gas chromatography/mass spectrometry (GC/MS) analysis has been developed to gain insight into the degradation of the chemical warfare agent sulfur mustard in solution. Specifically, the described approach simplifies the sample preparation for GC/MS analysis to provide a rapid determination of changes in sulfur mustard abundance. These results were found to be consistent with those obtained using liquid-liquid extraction (LLE) GC/MS. The utility of the described approach was further demonstrated by the investigation of the degradation process in a complex matrix with surfactant added to assist solvation of sulfur mustard. A more rapid reduction in sulfur mustard abundance was observed using the HS-SPME approach with surfactant present and was similar to results from LLE experiments. Significantly, this study demonstrates that HS-SPME can simplify the sample preparation for GC/MS analysis to monitor changes in sulfur mustard abundance in solution more rapidly, and with less solvent and reagent usage than LLE.