Development of a rapid and sensitive SPE-LC-MS/MS method for the simultaneous estimation of fluoxetine and olanzapine in human plasma

A high‐performance liquid chromatographic assay with tandem mass spectrometric detection was developed to simultaneously quantify fluoxetine and olanzapine in human plasma. The analytes and the internal standard (IS) duloxetine were extracted from 500 μL aliquots of human plasma through solid‐phase extraction. Chromatographic separation was achieved in a run time of 4.0 min on a Hypersil Gold C₁₈ column (50 × 4.6 mm, 5 µm) using isocratic mobile phase consisting of acetonitrile–water containing 2% formic acid (70:30, v/v), at a flow‐rate of 0.5 mL/min. Detection of analytes and internal standard was performed by electrospray ionization tandem mass spectrometry, operating in positive‐ion and multiple reaction monitoring acquisition mode. The protonated precursor to product ion transitions monitored for fluoxetine, olanzapine and IS were m/z 310.01 → 147.69, 313.15 → 256.14 and 298.1 → 153.97, respectively. The method was validated over the concentration range of 1.00–150.20 ng/mL for fluoxetine and 0.12–25.03 ng/mL for olanzapine in human plasma. The intra‐batch and inter‐batch precision (%CV) across four quality control levels was ≤6.28% for both the analytes. In conclusion, a simple and sensitive analytical method was developed and validated in human plasma. This method is suitable for measuring accurate plasma concentration in bioequivalence study and therapeutic drug monitoring as well, following combined administration. Copyright © 2011 John Wiley & Sons, Ltd.     

超高效液相色谱-串联质谱法测定血浆与尿液中14种麻痹性贝类毒素北大核心CSCD

人体生物基质中麻痹性贝类毒素的检测对其引起的食物中毒诊断和救治具有重要意义。研究建立了超高效液相色谱-串联质谱法测定血浆、尿液中14种麻痹性贝类毒素的分析方法。实验比较了不同固相萃取柱的影响,优化了前处理条件和色谱条件,血浆样品采用0.2 mL水、0.4 mL甲醇、0.6 mL乙腈提取后直接上机测定,尿液样品采用0.2 mL水、0.4 mL甲醇、0.6 mL乙腈提取,聚酰胺(PA)固相萃取柱净化后上机测定。采用Poroshell 120 HILIC-Z色谱柱(100 mm×2.1 mm,2.7μm)对14种贝类毒素进行分离,流动相为含0.1%(v/v)甲酸的5 mmoL/L甲酸铵缓冲溶液和0.1%(v/v)甲酸乙腈溶液,流速为0.50 mL/min。在电喷雾模式(ESI)下进行正负离子扫描,采用多反应监测(MRM)模式检测,外标法定量。结果表明,对于血浆和尿液样品,14种贝类毒素分别在0.24~84.06 ng/mL范围内线性关系良好,相关系数均大于0.995。尿液检测的定量限为4.80~34.40 ng/mL,血浆检测的定量限为1.68~12.04 ng/mL。尿液和血浆样品在1、2和10倍定量限加标水平下平均回收率为70.4%~123.4%,日内精密度为2.3%~19.1%,日间精密度为4.0%~16.2%。应用建立的方法对腹腔注射14种贝类毒素小鼠血浆和尿液进行测定,20份血浆样本中检出含量分别为19.40~55.60μg/L和8.75~13.86μg/L。该方法操作简便,样品取样量少,方法灵敏度高,适用于血浆和尿液中麻痹性贝类毒素的快速检测。     

Drug screening in human plasma by cloud-point extraction and HPLC

Cloud-point extraction (CPE) with RP-HPLC/DAD detection was used to develop a screen for six model basic drugs (paracetamol, promazine, amitriptyline, nortriptyline, clomipramine and chlorpromazine) in human plasma. These drugs’ varied hydrophobicities entail different affinities for the micelle-rich phase and CPE extraction efficiencies. Extraction recovery (except paracetamol) was above 80% and reproducibility (RSD%) ranged from 2.88 to 10.26 intraday and from 3.12 to 12.33 interday. The limits of detection were: 0.125 μg mL^?1 (promazine and chlorpromazine), 0.25 μg mL^?1 (amitriptyline and nortriptyline) and 0.5 μg mL^?1 (paracetamol and clomipramine). The method was linear over the ranges: 0.125–1.0 μg mL^?1 (promazine and chlorpromazine), 0.25–1.0 μg mL^?1 (amitriptyline and nortriptyline), 0.5–1.0 μg mL^?1 (clomipramine) and 0.5–10 μg mL^?1 (paracetamol). The procedure is a good alternative to the SPE or LLE sample preparation usually used.     

Optimization of alcohol‐assisted dispersive liquid–liquid microextraction by experimental design for the rapid determination of fluoxetine in biological samples

A sensitive and rapid method based on alcohol‐assisted dispersive liquid–liquid microextraction followed by high‐performance liquid chromatography for the determination of fluoxetine in human plasma and urine samples was developed. The effects of six parameters on the extraction recovery were investigated and optimized utilizing Plackett–Burman design and Box–Benken design, respectively. According to the Plackett–Burman design results, the volume of disperser solvent, extraction time, and stirring speed had no effect on the recovery of fluoxetine. The optimized conditions included a mixture of 172 μL of 1‐octanol as extraction solvent and 400 μL of methanol as disperser solvent, pH of 11.3 and 0% w/v of salt in the sample solution. Replicating the experiment in optimized condition for five times, gave the average extraction recoveries equal to 90.15%. The detection limit of fluoxetine in human plasma was obtained 3 ng/mL, and the linearity was in the range of 10–1200 ng/mL. The corresponding values for human urine were 4.2 ng/mL with the linearity range from 10 to 2000 ng/mL. Relative standard deviations for intra and inter day extraction of fluoxetine were less than 7% in five measurements. The developed method was successfully applied for the determination of fluoxetine in human plasma and urine samples.     

Determination of tricyclic antidepressants in human plasma using pipette tip solid-phase extraction and gas chromatography-mass spectrometry

A method for the simultaneous extraction of four tricyclic antidepressants from human plasma samples using pipette tip SPE with MonoTip C(18) tips is presented. Human plasma (0.1 mL) containing four tricyclic antidepressants (amitriptyline, amoxapine, imipramine, and trimipramine) and an internal standard (IS), protriptyline, was mixed with 0.4 mL of distilled water and 100 microL 1 M NaOH solution. After centrifugation of the mixture, the supernatant was extracted to the C(18) phase of the tip by 20 repeated aspirating/dispensing cycles using a manual micropipettor. The analytes retained in the tip were eluted with methanol by five repeated aspirating/dispensing cycles. Without evaporation and reconstitution, the eluate was directly injected into a gas chromatograph injector and detected by a mass spectrometer with SIM in the positive-ion electron impact mode. Recovery of the four antidepressants and IS spiked into human plasma was 80.2-92.1%. The regression equations for the four antidepressants showed excellent linearity in the range of 0.2-40 ng/0.1 mL. LODs and LOQs for the four drugs were 0.05-0.2 ng/0.1 mL and 0.2-0.5 ng/0.1 mL, respectively. Intra- and interday CVs for the four drugs in plasma were no greater than 9.5%.     

Development and validation of a rapid ultra high performance liquid chromatography with tandem mass spectrometry method for the simultaneous determination of darunavir,ritonavir, and tenofovir in human plasma: Application to human pharmacokinetics

A sensitive ultra high performance liquid chromatography with tandem mass spectrometry method was developed for the simultaneous determination of darunavir, ritonavir and tenofovir in human plasma. Sample preparation involved a simple liquid–liquid extraction using 200 μL of human plasma extracted with methyl tert‐butyl ether for three analytes and internal standard. The separation was accomplished on an Acquity UPLC BEH C₁₈ (50 mm x 2.1 mm, 1.7 μm) analytical column using gradient elution of acetonitrile/methanol (80:20, v/v) and 5.0 mM ammonium acetate containing 0.01% formic acid at a flow rate of 0.4 mL/min. The linearity of the method ranged between 20.0 and 12 000 ng/mL for darunavir, 2.0 and 2280 ng/mL for ritonavir, and 14.0 and 1600 ng/mL for tenofovir using 200 μL of plasma. The method was completely validated for its selectivity, sensitivity, linearity, precision and accuracy, recovery, matrix effect, stability, and dilution integrity. The extraction recoveries were consistent and ranged between 79.91 and 90.04% for all three analytes and internal standard. The method exhibited good intra‐day and inter‐day precision between 1.78 and 6.27%. Finally the method was successfully applied for human pharmacokinetic study in eight healthy male volunteers after the oral administration of 600 mg darunavir along with 100 mg ritonavir and 100 mg tenofovir as boosters.     

A simplified method for therapeutic drug monitoring of mitotane by gas chromatography-electron ionization-mass spectrometry

Mitotane is a key drug for the treatment of adrenal cortical carcinoma. Due to its narrow therapeutic window, 14–20 μg/mL, monitoring its concentration is crucially important. In this study, a simplified method for measuring mitotane in plasma using gas chromatography-electron ionization-mass spectrometry (GC-EI-MS) was developed. Through deproteination and liquid–liquid extraction, mitotane and an internal standard (IS) were extracted from plasma samples. GC-EI-MS yielded retention times of 8.2 and 8.7 min, for mitotane and the IS, respectively, with a total run time of 12 min. Selectivity and intra-/inter-batch accuracy and precision analyses provided a lower limit of quantification of 0.25 μg/mL, and a calibration curve between 0.25 and 40 μg/mL had good linearity (coefficient of determination = 0.992). The matrix effect factor and percent recovery of the method had good precision. Additionally, long-term sample stability was observed below 4°C. In a clinical setting, mitotane levels in plasma from an adrenal cortical carcinoma patient were within calibration range. Therefore, this simplified method can be applied to routine therapeutic drug monitoring of mitotane, which may contribute to improved treatment of adrenal cortical carcinoma.     

Quantitative determination of risperidone,paliperidone and olanzapine in human serum by liquid chromatography–tandem mass spectrometry coupled with on‐line solid‐phase extraction

A recent guideline recommends therapeutic drug monitoring for risperidone, paliperidone and olanzapine, which are frequently used second‐generation antipsychotics. We developed a simple high‐performance liquid chromatography–tandem mass spectrometry coupled with an online solid‐phase extraction method that can be used to measure risperidone, paliperidone and olanzapine using small (40 μL) samples. The analytes were extracted from serum samples automatically pre‐concentrated and purified by C₈ (5 μm, 2.1 × 30 mm) solid‐phase extraction cartridges, then chromatographed on an Xbidge™ C₁₈ column (3.5 μm, 100 × 2.1 mm) thermostatted at 30°C with a mobile phase consisting of 70% acetonitrile and 30% ammonium hydroxide 1% solution at an isocratic flow rate of 0.3 mL/min, and detected with tandem mass spectrometry. The assay was validated in the concentration range from 2.5 to 160 ng/mL. Intra‐ and inter‐day precision for all analytes was between 1.1 and 8.2%; method accuracy was between 6.6 and 7.6%. The risperidone and paliperidone assay was compared with a high‐performance liquid chromatography‐ultraviolet assay currently used in our hospital for risperidone and paliperidone therapeutic drug monitoring, and the results of weighted Deming regression analysis showed good agreement. For the olanzapine assay, we compared 20 samples in separate re‐assays on different days; all the relative errors were within the 20% recommended limit.     

Ionic liquid-based dispersive liquid-liquid microextraction for sensitive determination of aromatic amines in environmental water

Ionic liquid-based dispersive liquid-liquid microextraction was developed for the extraction and preconcentration of aromatic amine from environmental water. A suitable mixture of extraction solvent (100 μL, 1-butyl-3-methylimidazolium hexafluorophoshate) and dispersive solvent (750 μL, methanol) were injected into the aqueous samples (10.00 mL), forming a cloudy solution. After centrifuging, enriched analytes in the sediment phase were determined by HPLC-UV. The effect of various factors, such as the extraction and dispersive solvent, sample pH, extraction time and salt effect were investigated. Under optimum conditions, enrichment factors for 2-anilinoethanol, o-chloroaniline and 4-bromo-N,N-dimethylaniline were above 50 and the limits of detection (LODs) were 0.023, 0.015 and 0.026 ng/mL, respectively. Their linear ranges were 0.8-400 ng/mL for 2-anilinoethanol, 0.5-200 ng/mL for o-chloroaniline and 0.4-200 ng/mL for 4-bromo-N,N-dimethylaniline, respectively. Relative standard deviations (RSDs) were below 5.0%. The relative recoveries from samples of environmental water were in the range of 82.0-94.0%. Compared with other methods, dispersive liquid-liquid microextraction is simple, rapid, sensitive and economical.     

Determination of seven selected antipsychotic drugs in human plasma using microextraction in packed sorbent and gas chromatography–tandem mass spectrometry

A method using microextraction by packed sorbent (MEPS) and gas chromatography–tandem mass spectrometry (GC-MS/MS) is described for the determination of seven antipsychotic drugs in human plasma. The studied compounds were chlorpromazine (CPZ), haloperidol (HAL), cyamemazine, quetiapine, clozapine, olanzapine (OLZ), and levomepromazine; promazine, protriptyline, and deuterated CPZ were used as internal standards. The validation parameters included selectivity, linearity and limits of detection and quantitation, intra- and interday precision and trueness, recovery, and stability and were studied according to internationally accepted guidelines. The method was found to be linear between the lower limit of quantitation and 1000 ng/mL, except for OLZ and HAL (200 ng/mL), with determination coefficients higher than 0.99 for all analytes, and extraction efficiencies ranged from 62 to 92 %. Intra- and interday precision ranged from 0.24 to 10.67 %, while trueness was within a ±15 % interval from the nominal concentration for all analytes at all studied levels. MEPS has shown to be a rapid procedure for the determination of the selected antipsychotic drugs in human plasma, allowing reducing the handling time and the costs of analysis. Furthermore, GC-MS/MS has demonstrated to be a powerful tool for the simultaneous quantitation of the studied compounds, enabling obtaining adequate selectivity and sensitivity using a sample volume of as low as 0.25 mL.     

Electromembrane extraction of levamisole from human biological fluids

Electromembrane extraction coupled with high-performance liquid chromatography (HPLC) and ultraviolet (UV) detection was developed for the determination of levamisole in some human biological fluids. Levamisole migrated from 4 mL of different acidized biological matrices, through a thin layer of 2-nitrophenyl octyl ether containing 5% tris-(2-ethylhexyl) phosphate immobilized in the pores of a porous hollow fiber, into a 20-μL acidic aqueous acceptor solution present inside the lumen of the fiber. The parameters influencing electromigration were investigated and optimized. Within 15 min of operation at 200 V, levamisole was extracted from different biological fluid samples with recoveries in the range of 59-65%, which corresponded to preconcentration factors in the range of 118-130. The calibration curves showed linearity in the range of 0.5-10, 0.2-10 and 0.1-10 μg/mL for plasma, urine and saliva, respectively. Limits of detection of 0.1, 0.07 and 0.05 μg/mL and limits of quantification of 0.5, 0.2 and 0.1 μg/mL were obtained for plasma, urine and saliva, respectively. The relative standard deviations of the analysis were found to be in the range of 5.6-9.7% (n = 3). Electromembrane extraction was successfully processed for determination of levamisole in plasma, urine and saliva samples.     

Quantitative determination of imatinib in human plasma with high-performance liquid chromatography and ultraviolet detection

A simple and sensitive high-performance liquid chromatography (HPLC) method was developed to quantitate imatinib in human plasma. Imatinib and the internal standard dasatinib were separated using a mobile phase of 0.5% KH(2)PO(4) (pH3.5)-acetonitrile-methanol (55:25:20, v/v/v) on a CAPCELL PAK C18 MG II column (250 mm × 4.6 mm) at a flow rate of 0.5 mL/min and measurement at UV 265 nm. Analysis required 100 μL of plasma and involved a solid phase extraction with an Oasis HLB cartridge, which gave recoveries of imatinib from 73% to 76%. The lower limit of quantification for imatinib was 10 ng/mL. The linear range of this assay was between 10 and 5000 ng/mL (regression line r(2) > 0.9992). Inter- and intra-day coefficients of variation were less than 11.9% and accuracies were within 8.3% over the linear range. The plasma concentrations of imatinib obtained by our present method were almost the same as those assayed by an LC-MS-MS method at the Toray Research Center, Inc. This method can be applied effectively to measure imatinib concentrations in clinical samples.     

Determination of haloperidol in biological samples with the aid of ultrasound‐assisted emulsification microextraction followed by HPLC‐DAD

A rapid and simple quantitative method for preconcentration and determination of haloperidol in biological samples was developed using ultrasound‐assisted emulsification microextraction, based on the solidification of floating organic droplet combined with HPLC‐DAD. The effects of several factors were investigated. A total of 30 μL of 1‐undecanol as an extraction solvent was injected slowly into a glass‐centrifuge tube containing 4 mL alkaline sample solution that was located inside the ultrasonic water bath. The formed emulsion was centrifuged and the fine droplets of solvent were floated at the top of the test tube, then it was cooled in an ice bath and the solidified solvent was transferred into a conical vial, after melt, the analysis of the extract was carried out by HPLC. Under the optimal conditions, the extraction efficiencies were more than 90% and the preconcentration factors were obtained between 119–122. The LOQs were obtained between 4–8 μg/L and the calibration curves were linear within the range of 4–1000 μg/L. Finally this method was applied to the determination of haloperidol in plasma and urine samples in the range of μg/L and satisfactory results were achieved (RSDs <7%).     

LC–MS/MS method for simultaneous determination of ramelteon and its metabolite M‐II in human plasma: Application to a clinical pharmacokinetic study in healthy Chinese volunteers

A sensitive liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS) method was developed and validated for the simultaneous determination of ramelteon and its active metabolite M‐II in human plasma. After extraction from 200 μL of plasma by protein precipitation, the analytes and internal standard (IS) diazepam were separated on a Hedera ODS‐2 (5 μm, 150 × 2.1 mm) column with a mobile phase consisted of methanol–0.1% formic acid in 10 mm ammonium acetate solution (85:15, v/v) delivered at a flow rate of 0.5 mL/min. Mass spectrometric detection was operated in positive multiple reaction monitoring mode. The calibration curves were linear over the concentration range of 0.0500–30.0 ng/mL for ramelteon and 1.00–250 ng/mL for M‐II, respectively. This method was successfully applied to a clinical pharmacokinetic study in healthy Chinese volunteers after a single oral administration of ramelteon. The maximum plasma concentration (C_max), the time to the C_max and the elimination half‐life for ramelteon were 4.50 ± 4.64ng/mL, 0.8 ± 0.4h and 1.0 ± 0.9 h, respectively, and for M‐II were 136 ± 36 ng/mL, 1.1 ± 0.5 h, 2.1 ± 0.4 h, respectively.     

Determination of olanzapine for therapeutic drug monitoring in schizophrenia patients by LC/MS method

Olanzapine is an atypical antipsychotic drug from the thienobenzodiazepine family which displays efficacy in patients with schizophrenia and related psychoses. A novel LC/MS method was developed and validated for determination of olanzapine in schizophrenia patients' plasma. A liquid–liquid extraction procedure was carried out using 5 mL diethyl ether–diisopropyl ether mixture (1:1, v/v). Average recovery of the extraction procedure was 94.8%. Chromatographic separation was performed on reversed‐phase C₁₈ column (250 × 2.0 mm, 5 μm) using mixture of deionized water (trifluoro acetic acid 0.1%)–acetonitrile (20:80, v/v) as mobile phase at a flow rate of 1 mL/min. Irbesartan was used as internal standart and total run time was 2.5 min. Mass spectrometric analysis were carried out in selective‐ion montoring mode, and detected olanzapine at m/z 313.1 and IS at m/z 429.4 in all forms of the ions. The calibration curve of olanzapine was linear in the range 2–300 ng/mL (r² > 0.9993). The interday and intraday precisions (RSD) were <7.55%, and accuracy was >7.59% (n = 6). The proposed study was successfully validated with respect to the US Food and Drug Administration guidelines.     

Study on Determination of Six Transition Metal Ions in Biological Samples by SPE and RP‐HPLC

This paper reports the utilization of solid phase extraction and the reversed‐phase high‐performance liquid chromatography (RP‐HPLC) for the determination of six transition metal ions (iron, cobalt, nickel, copper, zinc and manganese) in biological samples. The samples were digested by microwave digestion. The iron, cobalt, nickel, copper, zinc and manganese ions in the digested samples can react with 2‐(2‐quinolinylazo)‐5‐diethylaminophenol (QADEAP) to form colored chelates in pH 4.0 acetic acid‐sodium acetic buffer solutions and cetyl trimethylammonium bromide (CTMAB) medium. These chelates were enriched by solid phase extraction with C₁₈ cartridge. Then the chelates were separated on a Waters Nova‐Pak‐C₁₈ column (3.9 × 150 mm, 5 μm) by gradient elution with methanol (containing 0.5% of acetic acid and 0.1% of CTMAB) and 0.05 mol/L pH 4.0 acetic acid‐sodium acetic buffer solution (containing 0.1% of CTMAB) as mobile phase at a flow rate of 0.5 mL/min. The detection limits of iron, cobalt, nickel, copper, zinc and manganese are 3 ng/L, 4 ng/L, 2 ng/L, 4 ng/L, 8 ng/L, 10 ng/L, respectively. This method was applied to the determination of iron, cobalt, nickel, copper, zinc and manganese in biological samples with good results.     

Preconcentration Ultra Trace of Cd(II) in Water Samples Using Dispersive Liquid‐Liquid Microextraction with Salen(N,N′‐Bis(Salicylidene)‐Ethylenediamine) and Determination Graphite Furnace Atomic Absorption Spectrometry

Dispersive liquid–liquid microextraction (DLLME) technique was successfully used as a sample preparation method for graphite furnace atomic absorption spectrometry (GF AAS). In this extraction method, 500 μL methanol (disperser solvent) containing 34 μL carbon tetrachloride (extraction solvent) and 0.00010 g Salen(N,N′‐bis(salicylidene)ethylenediamine) (chelating agent) was rapidly injected by syringe into the water sample containing cadmium ions (interest analyte). Thereby, a cloudy solution formed. The cloudy state resulted from the formation of fine droplets of carbon tetrachloride, which have been dispersed, in bulk aqueous sample. At this stage, cadmium reacts with Salen(N,N′‐bis(salicylidene)‐ethylenediamine), and therefore, hydrophobic complex forms which is extracted into the fine droplets of carbon tetrachloride. After centrifugation (2 min at 5000 rpm), these droplets were sedimented at the bottom of the conical test tube (25 ± 1 μL). Then a 20 μL of sedimented phase containing enriched analyte was determined by GF AAS. Some effective parameters on extraction and complex formation, such as extraction and disperser solvent type and their volume, extraction time, salt effect, pH and concentration of the chelating agent have been optimized. Under the optimum conditions, the enrichment factor 122 was obtained from only 5.00 mL of water sample. The calibration graph was linear in the range of 2‐21 ng L^?1 with a detection limit of 0.5 ng L^?1. The relative standard deviation (R.S.D._s) for ten replicate measurements of 20 ng L^?1 of cadmium was 2.9%. The relative recoveries of cadmium in tap, sea and rain water samples at a spiking level of 5 and 10 ng L^?1 are 99, 94, 97 and 96%, respectively. The characteristics of the proposed method have been compared with cloud point extraction (CPE), on‐line liquid‐liquid extraction, single drop microextraction (SDME), on‐line solid phase extraction (SPE) and co‐precipitation based on bibliographic data. Therefore, DLLME combined with GF AAS is a very simple, rapid and sensitive method, which requires low volume of sample (5.00 mL).     

A sensitive high performance liquid chromatography microassay for bemoradan, a novel cardiotonic agent, in plasma/serum using a semi-automatic liquid/solid extraction sample preparation system--AASP

A high performance liquid chromatographic method for the measurement of bemoradan levels in plasma/serum is described. This method uses Varian's AASP (Varian Associates, Sunnyvale, CA, USA), a semi-automatic liquid/solid extraction sample preparation system. It requires only small volumes of plasma/serum samples (0.2-1 mL) and needs no organic solvent for sample preparation. The mean recovery of bemoradan at plasma or serum concentrations of 0.5-100 ng/mL is 82%. The assay has a detection limit of 0.5 ng/mL (when 1 mL of plasma/serum is used) and is linear in the concentration range 0.5-500 ng/mL.     

Sorptive extraction with in-sample acetylation for gas chromatography-mass spectrometry determination of ethylphenol species in wine samples

An inexpensive and effective sample preparation procedure for the determination of three ethylphenolic off-flavours (4-ethylphenol, 4-ethylguaiacol and 4-ethylcathecol) in wine samples is presented. Analytes were in situ acetylated and concentrated using a disposable silicone sorbent (DSS) exposed to the diluted sample. After that, the analytes were recovered with ethyl acetate and determined by gas chromatography with mass spectrometry. The influence of different parameters (volume of acetic anhydride, basic catalyst, ionic strength, sorbent format, sampling mode and extraction time) on the efficiency of derivatization and extraction steps is discussed. Under optimized conditions, 2 mL of wine were diluted with 15 mL of an aqueous solution of potassium bicarbonate (5%, m/v) in a 22 mL vessel, containing 2 g of sodium chloride. The volume of acetic anhydride and the extraction time were set at 90 μL and 2 h, and the extraction was carried out at room temperature (20±2°C). Analytes were concentrated using a silicone disc (5 mm diameter × 0.5 mm thickness) and further desorbed with 0.2 mL of ethyl acetate. The achieved limits of quantification (LOQs), defined as the concentration of each compound providing a signal 10 times higher than the baseline noise, stayed between 5 and 15 ng mL(-1). The method provided a linear response range of up to 5000 ng mL(-1) and relative recoveries from 91% to 116%. The 4-ethylphenol off-flavour was detected in most red wine samples at concentrations of up to 2700 ng mL(-1).     

Utilization of an ionic liquid in situ preconcentration method for the determination of the 15 + 1 European Union polycyclic aromatic hydrocarbons in drinking water and fruit‐tea infusions

An ionic liquid (IL) in situ preconcentration method was optimized and applied to the monitoring of the 15 + 1 European Union polycyclic aromatic hydrocarbons in water and fruit‐tea infusions. The optimized method utilizes 10 mL of water (or infusion) containing 38 μL of the IL 1‐butyl‐3‐methylimidazolium chloride and a content of 36.1 g/L NaCl, which are mixed with Li‐NTf₂ (340 μL, 0.2 g/mL), followed by vortex (4 min) and centrifugation (5 min). The obtained microdroplet containing hydrocarbons is diluted with acetonitrile and injected into an HPLC with UV/Vis and fluorescence detection. The method presented average enrichment factors of 127 for water (tap water and bottled water) and 27 for two fruit‐tea infusions; with average relative recoveries of 86.7 and 106% for water and fruit‐tea infusions, respectively. The method was sensitive, with detection limits ranging from 0.001 to 0.050 ng/mL in water, and from 0.010 to 0.600 ng/mL in fruit‐tea infusions, for the fluorescent hydrocarbons. Real extraction efficiencies ranged from 12.7 to 58.7% for water, and from 20.2 to 117% for the infusions. The method was also fast (～12 min) and free of organic solvents in the extraction step.