Multi-residue determination of veterinary drugs in milk by ultra-high-pressure liquid chromatography-tandem mass spectrometry

Stir bar sorptive extraction with polyurethane (PU) and polydimethylsiloxane (PDMS) polymeric phases followed by high-performance liquid chromatography with diode array detection [SBSE(PU or PDMS)/HPLC-DAD] was studied for the determination of six acidic pharmaceuticals [o-acetylsalicylic acid (ACA), ibuprofen (IBU), diclofenac sodium (DIC), naproxen (NAP), mefenamic acid (MEF) and gemfibrozil (GEM)], selected as non-steroidal acidic anti-inflammatory drugs and lipid regulators model compounds in environmental water matrices. The main parameters affecting the efficiency of the proposed methodology are fully discussed. Assays performed on 25 mL of water samples spiked at the 10 microg L(-1) level under optimized experimental conditions, yielded recoveries ranging from 45.3+/-9.0% (ACA) to 90.6+/-7.2% (IBU) by SBSE(PU) and 9.8+/-1.6% (NAP) to 73.4+/-5.0% (GEM) by SBSE(PDMS), where the former polymeric phase presented a better affinity to extract these target analytes from water matrices at the trace level. The methodology showed also excellent linear dynamic ranges for the six acidic pharmaceuticals studied, with correlation coefficients higher than 0.9976, limits of detection and quantification between 0.40-1.7 microg L(-1) and 1.5-5.8 microg L(-1), respectively, and suitable precision (RSD <15%). Moreover, the developed methodology was applied for the determination of these target analytes in several environmental matrices, including river, sea and wastewater samples, having achieved good performance and moderate matrix effects. In short, the PU foams demonstrated to be an excellent alternative for the enrichment of the more polar metabolites from water matrices by SBSE, overcoming the limitations of the conventional PDMS phase.     

Direct enrichment of phenols in lake and sea water by stir bar sorptive extraction based on poly (vinylpyridine-ethylene dimethacrylate) monolithic material and liquid chromatographic analysis

A poly (vinylpyridine-ethylene dimethacrylate) monolithic material was synthesized and selected as stir bar sorptive extraction (SBSE) medium. The influences of polymerization conditions on the extraction efficiency were investigated using phenol and p-nitrophenol as target analytes. Based on this, six strongly polar phenols in water were directly concentrated by the new SBSE and determined with high performance liquid chromatography equipped with diode array detector. To achieve the optimum extraction performance, several main parameters, including extraction and desorption time, pH value and contents of inorganic salt in the sample matrix were investigated. The method showed good linearity and acceptable recoveries, as well as advantages such as sensitivity, simplicity, low cost and high feasibility. The proposed method was successfully applied to the determination of phenolic compounds in lake and sea waters.     

Simultaneous determination of alkylphenols and bisphenol A in river water by stir bar sorptive extraction with in situ acetylation and thermal desorption-gas chromatography-mass spectrometry

A method for the determination of seven alkylphenols and bisphenol A by stir bar sorptive extraction (SBSE) with in situ derivatization-thermal desorption (TD)-gas chromatography (GC)-mass spectrometry (MS) is described. SBSE was performed with in situ acetylation and without derivatization for comparison. For 4-tert-butylphenol and bisphenol A, in situ acetylation improved the responses in SBSE-TD-GC-MS. The method detection limits ranged from 0.1 to 3.2 ng/l. The recoveries of the analytes from a river water sample spiked with standards at 10 and 100 ng/l were 85.3-105.9% (R.S.D., 3.0-11.0%) and 88.3-105.8% (R.S.D., 1.6-8.3%), respectively.     

Optimisation of stir bar sorptive extraction and in-tube derivatisation-thermal desorption-gas chromatography-mass spectrometry for the determination of several endocrine disruptor compounds in environmental water samples

The analysis of organic pollutants in environmental water samples requires a pre-concentration step. Pre-concentration techniques such as stir bar sorptive extraction (SBSE) have gained popularity since they minimise the use of toxic organic solvents and can be considered as green analytical techniques. Similar to other pre-concentration techniques, one of the problems when SBSE is used is the matrix effect, which often occurs during the analysis of environmental water samples such as estuarine or wastewater samples. The present work studied the matrix effect during SBSE coupled to in-tube derivatisation–thermal desorption (TD)–gas chromatography–mass spectrometry for the determination of several endocrine disruptor compounds, such as alkylphenols, bisphenol A, estrogens and sterols, in environmental water samples, after optimisation of the major variables affecting the determination. Variables such as the addition of methanol or an inert salt to the donor phase, the extraction temperature, the volume of the donor phase, the stirring rate and the extraction time were studied during the SBSE optimisation. In the case of the in-tube derivatisation and TD step, the volume of the derivatisation reagent (N,O-bis(trimethylsilyl)triufloroacetamide with 1% of trimethylchlorosilane (BSTFA + 1% TMCS)) and the cryo-focusing temperature were fixed (2 μL and −50 °C, respectively) according to a consensus between maximum signal and optimal operation conditions. Good apparent recovery values (78–124%) were obtained for most of the analytes in Milli-Q water, except for 4-tert-octylphenol (4-tOP), which showed apparent recovery values exceeding 100%. Precision (n = 4) was in the 2–27%, and method detection limits were in the low nanogrammes per litre level for most of the analytes studied. The matrix effect was studied using two different approaches. On the one hand, Milli-Q water samples were spiked with humic acids, and apparent recovery values were studied with and without correction with the corresponding deuterated analogue. On the other hand, estuarine water and wastewater samples were spiked with known concentrations of target analytes, and apparent recoveries were studied as explained above. In general, the matrix effect could be corrected with the use of deuterated analogues, except for 4-tOP and nonylphenols for which [²H₄]-n-nonylphenol did not provide good corrections.     

Sensitive determination of acidic drugs and triclosan in surface and wastewater by ion-pair reverse-phase liquid chromatography/tandem mass spectrometry

A new method is presented for the determination of 12 acidic pharmaceuticals (non-steroidal anti-inflammatory drugs and bezafibrate), including two metabolites from aqueous samples, together with triclosan as a personal care product. Ion-pair liquid chromatography (IP-LC) with electrospray ionisation tandem mass spectrometry (ESI-MS) in the negative ion mode was employed. The ion-pairing agent (tri-n-butylamine) increased the signal intensity for all acidic analytes and detection limits of 6-200 ng/L were obtained by multiple reaction monitoring. This allows analysis of wastewater samples by direct injection into the LC/MS system without the need for a preceding enrichment step. When combined with a solid-phase extraction (SPE) step, limits of quantification between 0.15 and 11 ng/L were obtained from 100-mL sample volumes, which is adequate for most applications. The occurrence of matrix effects was studied and standard addition was required for reliable quantification after SPE from wastewater. The method was finally applied to surface and wastewaters, with analyte concentrations ranging from below the detection limit up to 5.5 microg/L.     

On-line solid-phase microextraction of triclosan, bisphenol A, chlorophenols, and selected pharmaceuticals in environmental water samples by high-performance liquid chromatography–ultraviolet detection

A method using on-line solid-phase microextraction (SPME) on a carbowax-templated fiber followed by liquid chromatography (LC) with ultraviolet (UV) detection was developed for the determination of triclosan in environmental water samples. Along with triclosan, other selected phenolic compounds, bisphenol A, and acidic pharmaceuticals were studied. Previous SPME/LC or stir-bar sorptive extraction/LC-UV for polar analytes showed lack of sensitivity. In this study, the calculated octanol–water distribution coefficient (log D) values of the target analytes at different pH values were used to estimate polarity of the analytes. The lack of sensitivity observed in earlier studies is identified as a lack of desorption by strong polar–polar interactions between analyte and solid-phase. Calculated log D values were useful to understand or predict the interaction between analyte and solid phase. Under the optimized conditions, the method detection limit of selected analytes by using on-line SPME-LC-UV method ranged from 5 to 33 ng?L^?1, except for very polar 3-chlorophenol and 2,4-dichlorophenol which was obscured in wastewater samples by an interfering substance. This level of detection represented a remarkable improvement over the conventional existing methods. The on-line SPME-LC-UV method, which did not require derivatization of analytes, was applied to the determination of TCS including phenolic compounds and acidic pharmaceuticals in tap water and river water and municipal wastewater samples.

Membrane-assisted solvent extraction of seven phenols combined with large volume injection-gas chromatography-mass spectrometric detection

Membrane-assisted solvent extraction (MASE) was applied for the determination of seven phenols (phenol, 2-chlorophenol, 2,4-dimethylphenol, 2,4-dichlorophenol, 4-chloro-3-methylphenol, 2,4,6-trichlorophenol and pentachlorophenol) with log Kow (octanol-water-partition-coefficient) between 1.46 (phenol) and 5.12 (pentachlorophenol) in water. The extraction solvents cyclohexane, ethyl acetate and chloroform were tested and ethyl acetate proved to be the best choice. The optimisation of extraction conditions showed the necessity of adding 5 g of sodium chloride to each aqueous sample to give a saturated solution (333 g/L). The pH-value of the sample was adjusted to 2 in order to convert all compounds into their neutral form. An extraction time of 60 min was found to be optimal. Under these conditions the recovery of phenol, the most polar compound, was 11%. The recoveries of the other analytes ranged between 42% (2-chlorophenol) and 98% (2,4-dichlorophenol). Calibration was performed using large volume injection (100 microL injection volume). At optimised conditions the limits of detection were between 0.01 and 0.6 microg/L and the relative standard deviation (n = 3) was on average about 10%. After the method optimisation with reagent water membrane-assisted solvent extraction was applied to two contaminated ground water samples from the region of Bitterfeld in Saxony-Anhalt, Germany. The results demonstrate the good applicability of membrane-assisted solvent extraction for polar analytes like phenols, without the necessity of derivatisation or a difficult and time-consuming sample preparation.     

Coupling of stir bar sorptive extraction with single photon ionization mass spectrometry for determination of volatile organic compounds in water

A home-made stir bar sorptive extraction (SBSE) apparatus was combined to a single photon ionization time-of-flight mass spectrometer (SPI-TOFMS) for rapid and sensitive determination of trace volatile organic compounds (VOCs) in water. The home-made SBSE bar, low-cost and disposable, was used for VOCs extraction. A thermal desorption (TD) device was designed to desorb the analytes from the SBSE bar, and a high throughput interface was developed to transfer the analytes into the ionization chamber of the SPI-TOFMS. The combination of large extraction volume of SBSE bar, and the direct measurement power of SPI-TOFMS enable a short analysis time for VOCs in water with high sensitivity, for example the limits of detection (LODs) were in the range of 7.4-11.1 ng L(-1) for benzene, toluene, and p-xylene (BTX) within 15 min. BTX aqueous solutions were chosen to demonstrate the quantitative capability, the linear range was from 0.05 to 100 μg L(-1) and the correlation coefficients were better than 0.996. The proposed method was successfully applied for the analysis of VOCs in urban river water.     

Determination of stale-flavor carbonyl compounds in beer by stir bar sorptive extraction with in-situ derivatization and thermal desorption-gas chromatography-mass spectrometry

A method for the determination of stale-flavor carbonyl compounds including E-2-octenal, E-2-nonenal, E,Z-2,6-nonadienal and E,E-2,4-decadienal in beer was developed using stir bar sorptive extraction (SBSE) with in-situ derivatization followed by thermal desorption-GC-MS analysis. The derivatization conditions with O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine and the SBSE conditions--sampling mode, salt addition, sample volume, polydimethylsiloxane volume (sample/polydimethylsiloxane phase ratio) and extraction time--were examined. The method showed good linearity over the concentration range from 0.1 to 10 ng ml(-1) for all analytes and the correlation coefficients were higher than 0.9993. The limits of detection ranged from 0.021 to 0.032 ng ml(-1) for all analytes. The recoveries (98-101%) and precision (RSD 2.4-7.3%) of the method were examined by analyzing beer samples fortified at the 0.5-ng ml(-1) level. The method was successfully applied to low-level concentration samples.     

Stir bar sorptive extraction and comprehensive two-dimensional gas chromatography coupled to high-resolution time-of-flight mass spectrometry for ultra-trace analysis of organochlorine pesticides in river water

A method for the determination of ultra-trace amounts of organochlorine pesticides (OCPs) in river water was developed by using stir bar sorptive extraction (SBSE) followed by thermal desorption and comprehensive two-dimensional gas chromatography coupled to high-resolution time-of-flight mass spectrometry (SBSE-TD-GC×GC-HRTOF-MS). SBSE conditions such as extraction time profiles, phase ratio (β: sample volume/polydimethylsiloxane (PDMS) volume), and modifier addition, were examined. Fifty milli-liter sample including 10% acetone was extracted for 3 h using stir bars with a length of 20 mm and coated with a 0.5 mm layer of PDMS (PDMS volume, 47 μL). The stir bar was thermally desorbed and subsequently analyzed by GC×GC-HRTOF-MS. The method showed good linearity over the concentration range from 50 to 1000 pg L(-1) or 2000 pg L(-1) for all analytes, and the correlation coefficients (r(2)) were greater than 0.9903 (except for β-HCH, r(2)=0.9870). The limit of detection (LOD) ranged from 10 to 44 pg L(-1). The method was successfully applied to the determination of 16 OCPs at pg L(-1) to ng L(-1) in river water. The results agree fairly well with the values obtained by a conventional liquid-liquid extraction (LLE)-GC-HRMS (selected ion monitoring: SIM) method using large sample volume (20 L). The method also allows screening of non-target compounds, e.g. pesticides and their degradation products, polyaromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), and pharmaceuticals and personal care products (PPCPs) and metabolites in the same river water sample, by using full spectrum acquisition with accurate mass in GC×GC.     

Simultaneous solid-phase extraction of acidic, neutral and basic pharmaceuticals from aqueous samples at ambient (neutral) pH and their determination by gas chromatography-mass spectrometry

Seven polymeric solid-phase extraction (SPE) sorbents were evaluated with regard to their ability to extract acidic, neutral and basic pharmaceuticals and estrogens simultaneously from water at neutral pH. Highest recoveries (70-100%) for the majority of the analytes were obtained with styrene-methacrylate and styrene-N-vinylpyrrolidone co-polymers. The latter one (Oasis HLB) was chosen for further refinement of an extraction method for the quantitative determination of acidic and neutral drugs in surface water samples at detection limits below 1 ng/l. A sequential elution protocol was applied for clean-up and separation of the extracted analytes into fractions suitable for further compound specific processing. The neutral analytes as well as the acidic compounds after derivatisation were quantified by GC-MS. Caffeine, ibuprofen, its metabolites and diclofenac were detected in river water samples in the 1-100 ng/l range.     

Evaluation of a new solid-phase cartridge for the preconcentration of phenolic compounds in water

The aim of this study is to evaluate the efficiency of a new solid-phase extraction cartridge, Spe-ed Advanta, in the extraction and preconcentration of four phenolic compounds (phenol, 2-chlorophenol, 2-nitrophenol, and 2,4-dichlorophenol) from water. The solid phase is a polystyrene-divinylbenzene resin modified with carboxylic groups, these polar groups improve the contact between the matrix and the aqueous solutions in the extraction of polar analytes. We studied several elution solvents in order to find the most efficient one. Sample concentration, sample volume, and sample pH are also investigated as well as the best method for drying the cartridge. Recoveries achieved with the new phase are compared with those obtained with Isolute ENV+, a non-modified polystyrene-divinylbenzene stationary bed. The best experimental conditions were then used for determination of the phenols in spiked environmental waters.     

Multiresidue fully automated online SPE-HPLC-MS/MS method for the quantification of endocrine-disrupting and pharmaceutical compounds at trace level in surface water

The present work describes the development and validation of a sensitive method for the determination of traces of diverse groups of pharmaceuticals and endocrine disruptors in surface water. Thirty-seven substances have been selected, including 10 pesticides, 6 hormonal steroids and assimilates, 12 pharmaceuticals, 5 alkylphenols, 1 chlorophenol and 3 other well-known human contaminants, 1 UV filter and 2 plasticisers. An automated online solid-phase extraction (SPE) is directly coupled to liquid chromatography–tandem mass spectrometry. Different SPE columns have been tested, and the injection volume has been optimised. The developed analytical methodology is based on the direct injection of 2.5 mL of water sample acidified at pH 1.6 on an Oasis HLB loading column (20 × 2.1 mm) with 5-µm particles. Then, the chromatographic separation is achieved on a Kinetex XB C18 (100 × 2.1 mm; 1.7 µm) column, and the quantification is realised in multiple-reaction monitoring mode. The online SPE step warrants minimal sample handling, low solvent consumption, high sample throughput, saving time and costs. This method allows the quantification of the target analytes in the lower ng/L concentration range, with limits of quantification (LQs) between 100 pg/L and 10 ng/L, 26 compounds having LQ lower than 1 ng/L. The monitoring of two selected MS/MS transitions for each compound allows the reliable confirmation of positive findings even at the LQ level. The developed and validated methodology has been applied to the analysis of various real samples from two French rivers. Twelve target compounds have been detected in the environmental samples, and the major pollutants are pharmaceuticals usually used by humans (paracetamol, carbamazepine, oxazepam, ketoprofen, trimethoprim). The pesticides atrazine and carbendazim have been ubiquitously detected in real samples too. Metronidazole, sulfamethoxazole and diuron were also frequently quantified in the water samples.     

Development and validation of stir bar sorptive extraction of polar phenols in water followed by HPLC separation in poly(vinylpyrrolididone‐divinylbenzene) monolith

An effective and simple method for polar phenols in water matrix was developed by using stir bar sorptive extraction (SBSE) based on a hydrophilic poly(vinylpyrrolididone‐divinylbenzene) (VPDB) monolithic material and HPLC analysis. To achieve optimum extraction performance for phenols, several parameters, including extraction and desorption time, desorption solvent, pH value, and ionic strength of sample matrix, were investigated. Under the optimized experimental conditions, eight phenols were directly enriched from water samples and analyzed by HPLC‐DAD. The detection limits (S/N = 3) and quantification limits (S/N = 10) of the proposed method for the target compounds were achieved within the range of 0.72–1.37 and 2.40–4.27 ng/mL from spiked water, respectively. Recoveries of eight phenolic compounds were found in the range of 55.2–95.9%. The calibration curves showed the linearity ranging from 5 to 150 ng/mL with linear regression coefficient R² values above 0.98. Method repeatability presented as intra‐ and interday precisions were also found with the RSDs less than 4.10 and 7.61%, respectively. The distribution coefficients between VPDB and water (K_VPDB/W) for phenolic compounds were also calculated and compared with K_O/W. Finally, the proposed method was successfully applied to the determination of the target compounds in tap water, sea water and wastewater samples.     

Optimisation of stir bar sorptive extraction for the analysis of volatile phenols in wines

An easy, fast and reliable analytical method is proposed for the determination of the concentration of volatile phenols (ethyl- and vinylphenols) in wines. The novel stir bar sorptive extraction (SBSE) technique is employed, following a simple and fast procedure that allows 15 samples to be extracted simultaneously using very small sample volume. Extracts are desorbed in a thermodesorption system (TDS) coupled on-line to a gas chromatograph-mass spectrometry system. The SBSE offers better recovery and linear regression coefficient (r2) for the four volatile phenols than solid-phase extraction (SPE). The mass spectrometric detection in selected ion monitoring mode contributes to the lower detection limit and good sensibility obtained with this method.     

Stir bar sorptive extraction-thermal desorption-capillary GC-MS applied to biological fluids

A new sample preparation method, stir bar sorptive extraction (SBSE), has been evaluated for the enrichment of organic solutes from biological fluids such as urine and blood. In SBSE, a stir bar coated with a polydimethylsiloxane layer is stirred for a given time in the sample. After sampling the stir bar is placed in a thermal desorption unit coupled on-line to capillary gas chromatography-mass spectrometry (SBSE-TD-CGC-MS). The principle and operation of SBSE are presented. Total profiling and target compound analysis have been selected as applications to illustrate the performance of SBSE-TD-CGC-MS (MSD). It is demonstrated that a variety analytes ranging from biological markers (phenols, hormones, fatty acids) to artificial contaminants (recreational drugs, plasticizers) can be enriched with high sensitivity. For polar solutes, in-situ derivatization can enhance both recovery into the polydimethylsiloxane (PDMS) layer and chromatographic analysis. Two types of derivatization have been applied, derivatization with ethyl chloroformate and with acetic acid anhydride. Linearity, detectability, and repeatability are illustrated by the determination of 1-hydroxypyrene in a urine sample from a smoker.     

Strategies for the microextraction of polar organic contaminants in water samples

In this paper the most recent developments in the microextraction of polar analytes from aqueous environmental samples are critically reviewed. The particularities of different microextraction approaches, mainly solid-phase microextraction (SPME), stir-bar-sorptive extraction (SBSE), and liquid-phase microextraction (LPME), and their suitability for use in combination with chromatographic or electrically driven separation techniques for determination of polar species are discussed. The compatibility of microextraction techniques, especially SPME, with different derivatisation strategies enabling GC determination of polar analytes and improving their extractability is revised. In addition to the use of derivatisation reactions, the possibility of enhancing the yield of solid-phase microextraction methods for polar analytes by using new coatings and/or larger amounts of sorbent is also considered. Finally, attention is also focussed on describing the versatility of LPME in its different possible formats and its ability to improve selectivity in the extraction of polar analytes with acid-base properties by using separation membranes and buffer solutions, instead of organic solvents, as the acceptor solution.     

大体积搅拌棒吸附萃取技术与热脱附-气相色谱-质谱法测定地表水中多环芳烃

基于搅拌棒吸附萃取(SBSE)技术建立了气相色谱-质谱测定地表水中16种多环芳烃(PAHs)的分析方法。该法采用多搅拌吸附棒同时富集,依次热脱附冷聚焦后进样的方式有效解决了搅拌棒吸附时间长、富集水样体积小等问题。优化后的结果表明,在0.2~10 ng/L范围内(萘为0.5~10 ng/L范围),16种PAHs的线性关系良好,相关系数(r)均0.99,方法检出限(MDL)为0.03~0.20 ng/L(萘为0.50 ng/L)。用该方法对钱塘江流域地表水进行测定,共检测出11种PAHs,含量为0.13~1.57 ng/L,不同添加水平下的加标回收率为75.6%~108.9%。该法可应用于地表水样品中该类物质的超痕量检测。     

Sensitive determination of strongly polar aromatic amines in water samples by stir bar sorptive extraction based on poly(vinylimidazole-divinylbenzene) monolithic material and liquid chromatographic analysis

A simple and sensitive method for the determination of polar aromatic amines (PAAs) was developed using stir bar sorptive extraction (SBSE) coupling to high-performance liquid chromatography. A hydrophilic poly(vinylimidazole-divinylbenzene) (VIDB) monolithic material was prepared and acted as SBSE coating. The influences of polymerization conditions for VIDB on the extraction efficiency were investigated using aniline and 2,4-dinitroaniline as detected solutes. To achieve optimum extraction performance for PAAs, several parameters including extraction and desorption time, desorption solvent, ionic strength and pH value of sample matrix were investigated. The results showed that under the optimized experimental conditions, the method showed good sensitivity and excellent recoveries, as well as advantages such as linearity, simplicity, low cost and high feasibility. The extraction performance of present method to the target compounds also compared with commercial SBSE which using polydimethylsiloxane as coating and other SBSE which based on monolithic materials. Finally, the proposed method was successfully applied to the determination of PAAs in lake and sea waters, and excellent recoveries of spiked target compounds in real samples were obtained.     

Stir bar sorptive extraction based on restricted access material for the direct extraction of caffeine and metabolites in biological fluids

A biocompatible stir bar sorptive extraction (SBSE) device was prepared using an alkyl-diol-silica (ADS) restricted access material (RAM) as the SBSE coating. The RAM-SBSE bar was able to simultaneously fractionate the protein component from a biological sample, while directly extracting caffeine and its metabolites, overcoming the present disadvantages of direct sampling in biological matrices by SBSE, such as fouling of the extraction coating by proteins. Desorption of the analytes was performed by stirring the bar in a water/ACN mixture (3/1, v/v) and subsequently reconcentrating the sample solution in water to enable HPLC-UV analysis to be performed. The limit of detection, based on a signal to noise ratio of 3, for caffeine was 25 ng/mL in plasma. The method was confirmed to be linear over the range of 0.5-100 microg/mL of caffeine with an average linear coefficient (R2) value of 0.9981. The injection repeatability and intra-assay precision of the method were evaluated over ten injections, resulting in a %RSD of approximately 8%. The RAM-SBSE device was robust (>50 extraction in plasma without significant signal loss) and simple to use, providing many direct extractions and subsequent determination of caffeine and its metabolites in biological fluids. In contrast to existing sample preparation methods for the analysis of caffeine and selected metabolites in biological fluids, this feasibility study using a biocompatible SBSE approach was advantageous in terms of simplifying the sample preparation procedures.