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A chromatographic method involving a single run was validated for the quantification of clanobutin, dichlorvos, and naftazone in products of animal origin. Pork, beef, chicken, milk, and egg samples were extracted with a solution of 0.1% formic acid in acetonitrile, defatted with n-hexane, centrifuged, and filtered prior to analysis using liquid chromatography-tandem mass spectrometry (LC-/MS/MS). The analytes were separated on a C18 column using a solution of 0.1% formic acid and 10 mM ammonium formate (A) and acetonitrile (B) as the mobile phase. A good linearity over 5-50 ng/g concentration range was obtained with coefficients of determination (R 2 ) ≥ 0.9807. The intra- and interday accuracy (recovery %) calculated from 3 fortification levels (5, 10, and 20 ng/g) were 73.2-108.1% and 71.4-109.8%, and the precisions (expressed relative standard deviations (RSDs)) were 0.9-12.9% and 1.8-10.6%, respectively, for the 3 tested analytes in animal originated foods. The limits of quantification (LOQs) ranged between 0.1 and 1 ng/g, thus enabling the quantification of residual levels below the uniform maximum residue limit (MRL) of 0.01 mg/kg set for compounds having no MRL. The designated methodology was successfully applied to monitor various samples collected from Seoul; the tested analytes were not quantified in any of the market samples. Conclusively, the developed method is simple, sensitive, and accurate, and could be used for the detection of pharmaceuticals in various animal food matrices with variable protein and fat contents., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

An analytical method was developed for the detection of toldimfos sodium residues in porcine muscle and bovine milk using liquid chromatography-triple quadrupole tandem mass spectrometry (LC-MS/MS) analysis. The drug was extracted from muscle and milk using 10 mm ammonium formate in acetonitrile and then purified using n-hexane. The drug was well separated on a Luna C 18 column using a mixture of 10 mm ammonium formate in ultrapure water (A) and acetonitrile (B) as the mobile phase. Good linearity was achieved over the tested concentration range (0.005-0.03 mg/kg) in matrix-matched standard calibration. The determination coefficients (R 2 ) were 0.9942 and 0.9898 for muscle and milk, respectively. Fortified porcine muscle and bovine milk contained concentrations equivalent to and twice the limit of quantification (0.005 mg/kg) yielded recoveries in the range of 75.58-89.74% and relative standard deviations of ≤8.87%. Samples collected from large markets located in Seoul, Republic of Korea, tested negative for toldimfos sodium residue. In conclusion, ammonium formate in acetonitrile can effectively extract toldimfos sodium from porcine muscle and bovine milk without solid-phase extraction, which is usually required for cleanup before analysis. This method can be applied for the routine analysis of toldimfos in foods of animal origins., (Copyright © 2017 John Wiley & Sons, Ltd.)

In this study, a simple analytical approach has been developed and validated for the determination of bupivacaine hydrochloride and isoflupredone acetate residues in porcine muscle, beef, milk, egg, shrimp, flatfish, and eel using liquid chromatography-tandem mass spectrometry (LC-MS/MS). A 0.1% solution of acetic acid in acetonitrile combined with n-hexane was used for deproteinization and defatting of all tested matrices and the target drugs were well separated on a Waters Xbridge™ C18 analytical column using a mobile phase consisting of 0.1% acetic acid (A) and 0.1% solution of acetic acid in methanol (B). The linearity estimated from six-point matrix-matched calibrations was good, with coefficients of determination ≥0.9873. The limits of quantification (LOQs) for bupivacaine hydrochloride and isoflupredone acetate were 1 and 2ngg -1 , respectively. Recovery percentages in the ranges of 72.51-112.39% (bupivacaine hydrochloride) and 72.58-114.56% (isoflupredone acetate) were obtained from three different fortification concentrations with relative standard deviations (RSDs) of <15.14%. All samples for the experimental work and method application were collected from the local markets in Seoul, Republic of Korea, and none of them tested positive for the target drugs. In conclusion, a simple method using a 0.1% solution of acetic acid in acetonitrile and n-hexane followed by LC-MS/MS could effectively extract bupivacaine hydrochloride and isoflupredone acetate from porcine muscle, beef, milk, egg, shrimp, flatfish, and eel samples., (Copyright © 2017 Elsevier B.V. All rights reserved.)

A liquid chromatography-electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) method was developed for monitoring and detection of four different drugs, namely acetanilide, pentylenetetrazole, phenacetin, and tetramethrin in porcine muscle, pasteurized milk, and table egg samples. For acetanilide and pentylenetetrazole, the samples were extracted with 0.1 % formic acid in acetonitrile, followed by defatting with n-hexane, partitioning at -20 °C for 1 h, centrifugation, and filtration, whereas the quick, easy, cheap, effective, rugged, and safe "QuEChERS" method was used for phenacetin and tetramethrin. The final extracts were combined and analyzed in a single chromatographic run using an XBridge(TM) analytical column and 0.1 % formic acid and 10 mM ammonium formate in ultrapure water (A) and 0.1 % formic acid and 10 mM ammonium formate in methanol (B) as the mobile phase. Owing to the unavailability of internal standards, matrix-matched calibrations were used for analyte quantification with coefficients of determination (R (2)) ≥ 0.9865. The intra- and inter-day accuracies ranged from 60.75 to 90.90 % and from 63.75 to 89.30 %, respectively, while the respective analytical precisions were 1.48-17.44 % (23.3 % for porcine sample spiked with phenacetin) and 1.97-15.78 %. The limits of quantification (LOQ) were between 0.5 and 2.5 ng/g in the matrices tested. Food samples purchased from local markets in Seoul were analyzed using the developed method and none of the tested drugs was detected.

A simple analytical method based on liquid chromatography coupled with triple-quadrupole mass spectrometry was developed for detection of the veterinary drugs flumethasone, dl-methylephedrine, and 2-hydroxy-4,6-dimethylpyrimidine in porcine muscle and pasteurized cow milk. The target drugs were extracted from samples using 10mM ammonium formate in acetonitrile followed by clean-up with n-hexane and primary secondary amine sorbent (PSA). The analytes were separated on an XBridge™ hydrophilic interaction liquid chromatography (HILIC) column using 10mM ammonium formate in ultrapure water and acetonitrile. Good linearity was achieved over the tested concentrations in matrix-fortified calibrations with correlation coefficients (R(2))≥0.9686. Recovery at two spiking levels ranged between 73.62-112.70% with intra- and inter-day precisions of ≤20.33%. The limits of quantification ranged from 2-10ng/g in porcine muscle and pasteurized cow milk. A survey of market samples showed that none of them contained any of the target analytes. Liquid-liquid purification using n-hexane in combination with PSA efficiently removed the interferences during porcine and milk sample extraction. The developed method is sensitive and reliable for detection of the three target drugs in a single chromatographic run. Furthermore, it exhibits high selectivity and low quantification limits for animal-derived food products destined for human consumption., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Analysis of residual quantities of contaminants in foods of animal origin is crucial for quality control of consumer products. This study was aimed to develop a simple and raid analytical method for detection of tetramisole and diethylcarbamazine using gradient liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS). Tetramisole, diethylcarbamazine, and guaifenesin (as an internal standard) were extracted from milk, eggs, and porcine muscle using acetonitrile followed by partitioning at -20 °C for 1h. No extract purification was deemed necessary. The analytes were separated on C18 column using ammonium formate both in water and methanol. Good linearity was achieved over the tested concentration range with R(2) ⩾ 0.974. Recovery at two fortification levels ranged between 67.47% and 97.38%. The intra- and inter-day precisions were <20%. The limit of quantification was 0.2 and 2 ng/g for tetramisole and diethylcarbamazine, respectively. An analytical survey of samples purchased from large markets showed that none of the samples contained any of the target analytes. To the best of our knowledge, this is the first report on the quantitative determination of tetramisole and diethylcarbamazine in animal food products., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The concentrations of residual aminopyrine and antipyrine in porcine muscle, milk, and egg samples were analyzed using liquid chromatography with tandem mass spectrometry after undergoing a series of sample pretreatment steps. Owing to an ion suppression effect, matrix-matched calibrations were used for analyte quantitation with determination coefficients (R(2) ) ≥ 0.9931. The recovery rates for aminopyrine and antipyrine in various matrices at two spiking levels (5 and 10 ng/g) fell in the range of 60.96-68.87 and 61.87-66.99%, respectively. Meanwhile, the intra- and inter-day precisions (expressed as relative standard deviation) were 1.02-12.95 and 1.71-5.50%, respectively. The method's detection limit (1 ng/g) was very low, thus enabling the detection of low residue levels. The applicability of the developed method was demonstrated with actual market samples and none of the tested analytes was detected in any of the samples., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A multiclass, multiresidue determination method is reported for the detection of ten veterinary drugs, including scopolamine, metoclopramide, acriflavine, berberine, tripelennamine, diphenhydramine, acrinol, triamcinolone, loperamide, and roxithromycin in pork, milk, and eggs. The method involves a simple extraction using 0.1% formic acid in acetonitrile, followed by defatting with n-hexane, centrifugation, and filtration prior to liquid chromatography with tandem mass spectrometric analysis. As ion suppression and enhancement effects are reported, matrix-matched calibrations are used for quantification, with determination coefficients ≥0.9765. For the majority of the tested analytes, the intra- and interday accuracy (expressed as recovery %) range from 70.6 to 94.6% and from 70.1 to 93.3%, respectively, and the precision (expressed as relative standard deviation) ranges from 0.5 to 19.8% and from 2.8 to 18.4% in all matrices. The limits of quantification range between 0.5 and 10 ng/g. The validated tandem mass spectrometry method is successfully applied to market samples; the target analytes are not detected in any of the tested samples. In terms of accuracy, no extract cleanup is deemed necessary. The developed method is feasible for the simultaneous detection of the tested analytes in pork, milk, and eggs., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

In this work, a liquid chromatography-tandem mass spectrometric detection technique was developed and validated for the determination of brotizolam residues in beef muscle and commercial whole milk. This procedure involves the extraction of the analyte from the samples via liquid-solid extraction, and caffeine was used as an internal standard. The analyte was successfully separated on an XTerra-C(18) column, with a mobile phase composed of 0.01% formic acid in acetonitrile and 1 mm ammonium formate-0.01% formic acid in water. The one-step extraction method evidenced good selectivity, precision (RSD = 9.87-26.47%), and the recovery of the extractable analyte was 92.61-115.98% in the matrices. The limits of quantification ranged between 0.4 and 0.5 µg/kg. The developed method is simple since it requires no additional cleanup procedures., (Copyright © 2011 John Wiley & Sons, Ltd.)

In this study, a simplified method for the extraction and determination of seven fluoroquinolone residues (danofloxacin, difloxacin, enrofloxacin, marbofloxacin, orbifloxacin, ofloxacin, and sarafloxacin) and three quinolones (oxolinic acid, flumequine, and nalidixic acid), in porcine muscle, table eggs, and commercial whole milk, which required no cleanup step, was devised. This procedure involves the extraction of analytes from the samples via liquid-phase extraction, and the subsequent quantitative determination was accomplished via LC-fluorescence detection. Analyte separation was successfully conducted on an XBridge-C(18) column, with a linear gradient mobile phase composed of acetonitrile and 0.01 M oxalic acid buffer at pH=3.5. The one-step liquid-liquid extraction method evidenced good selectivity, precision (RSDs=0.26-15.07%), and recovery of the extractable analytes, ranging from 61.12 to 115.93% in matrices. The LOQs ranged from 0.3 to 25 microg/kg. A survey of ten samples purchased from local markets was conducted, and none of the samples harbored fluoroquinolone residues. This method is an improvement over existing methodologies, since no additional cleanup was necessary.

Since its extensive development in the early 1980s, SFE has attracted considerable attention as a sample-preparation procedure. However, other different sample preparation procedures, including precipitation, liquid- and/or solid-phase extraction in biological fluids, also remain in use. In this investigation, SFE was introduced to isolate and identify orbifloxacin from plasma and milk. Four parameters, including the temperature and the pressure of supercritical fluid, modifier ratios, and dynamic extraction time, were evaluated and optimized to obtain the best yield of the analyte from the biological fluids. Determinations of the orbifloxacin (OBFX) in the extracts were carried out using HPLC-FLD. The optimum conditions of the extraction process that yielded the maximum analyte extraction efficiencies were 150 degrees C vs. 60 degrees C, 250 kg cm(-2), 30% vs. 35% methanol, and 40 min vs. 20 min, for plasma and milk, respectively. The linearity of the calibration curves as well as the instrument LODs/LOQs were evaluated. Good linearity (at least r(2) > or = 0.999) of the calibration curves was obtained over the range from 0.2 to 0.01 microg mL(-1). The method showed a good recovery rate (74.2-127.73%) and precision (RSDs: 1.64-20%). The instrumental LOD and LOQ values were 0.004 microg mL(-1) vs. 0.01 microg mL(-1) or 0.006 microg mL(-1) vs. 0.02 microg mL(-1), for plasma and milk, respectively. The method was successfully applied to estimate the pharmacokinetic variables of orbifloxacin in lactating does. To the best of our knowledge, this is the first time that SFE has been applied to isolate an antimicrobial agent from biological fluids. This method is promising for clinical applications and for pharmacokinetic studies of various pharmaceuticals in biological fluids.

The principal goal of this work was to develop an efficient method for the simultaneous determination of four pyrethroid (PYR) insecticides, cyfluthrin, cyhalothrin, cypermethrin, and deltamethrin, in porcine muscle and pasteurized milk using liquid-liquid extraction (LLE). Sample extraction was carried out with and without additional column cleanup procedures, and the final determination was made using GC with electron-capture detector (ECD). The pesticide identity was confirmed using GC-MS in the SIM mode. Since there were minor differences between the extraction procedures, extraction without the additional cleanup procedure was used throughout the work. The method was validated by fortifying blank samples with half, two, and four times the maximum residue limit (MRL) of each PYR. The average recoveries (n = 6) ranged from 83.5 to 99.2% and 82.9 to 109% in porcine muscle and pasteurized milk, respectively. The repeatability of measurements expressed as RSDs, was in the range of 1.7-11.9 and 1.5-10.3% in porcine muscle and pasteurized milk, respectively. The LODs ranged from 3.3 to 9 and 3 to 8.1 ppm, whereas the LOQs ranged from 10 to 27.4 and 9 to 24.6 ppm, in porcine muscle and pasteurized milk, respectively. The applicability of the method was demonstrated by analyzing real samples collected from major cities in the Republic of Korea. No residues of the selected pesticides were detected in any of the samples.

Using the microbial inhibition test, the single-dose pharmacokinetics of pefloxacin mesylate dehydrate were studied in six clinically normal lactating she-camels (Camelus dromedarius) after intravenous (IV) and intramuscular (IM) administration of 10 mg/kg body weight (bwt). Blood and milk samples were collected intermittently for a 48 h period, and the pharmacokinetic variables were calculated using compartmental and non-compartmental analytical methods.The plasma course of pefloxacin was best resolved to a two-compartment open model after IV administration and a two-compartment open model with first-order absorption after IM administration. Pefloxacin exhibits a long elimination-phase disposition half-life (t1/2beta) of 4.89 +/- 1.12 h after IV injection and 5.73 +/- 1.42 h after IM administration. The mean volume of distribution at steady state (Vdss) and total body clearance (Cl(tot)) values after IV dosing were 1.18 +/- 0.45 I/kg and 0.21 +/- 0.10 I/kg/h, respectively. The observed peak plasma level (Cmax) of 3.6 +/- 0.1 microg/ml was rapidly attained at 0.75 h (the time of maximum concentration Tmax) after IM administration. The areas under the concentration versus time curves (AUCs) were 44.18 +/- 9.68 microg x h/ml and 29.42 +/-6.49 microg x h/ml after IV and IM administration, respectively. The absolute bioavailability (F%) obtained after IM administration was 71.59 +/- 12.45%. Milk was penetrated quickly, with a mean peak level of 3.24 +/- 0.17 microg/ml occurring at 1.0 h. The elimination half-life was significantly shorter after IV versus IM administration (4.21 +/- 0.84 h versus 5.32 +/- 0.67 h, respectively). Ultimately, pefloxacin could be useful for treatment of udder infections in she-camels after specific assessment of susceptible microorganisms.

Graphical abstract Highlights • A protocol was developed for detecting and quantifying scopolamine, L-hyoscyamine, and sparteine. • Target analytes were extracted from animal-based food using EN-QuEChERS and analyzed by LC-MS/MS. • EDTA solution was employed to improve recovery. • LOQ values of 1–5 µg/kg were obtained for all analytes. Abstract We developed a modified Quick, Easy, Cheap, Effective, Rugged, and Safe (CEN QuEChERS) extraction method coupled with liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI+/MS-MS) to identify and quantify residues of three botanical alkaloids, namely, scopolamine, L-hyoscyamine, and sparteine, in animal-derived foods, including porcine muscle, egg, and milk. A combination of ethylenediaminetetraacetic acid disodium buffer and acetonitrile acidified with 0.5% trifluoroacetic acid was used as an extraction solvent, whereas QuEChERS (CEN, 15662) kits and sorbents were applied for cleanup procedures. The proposed method was validated by determining the limits of quantification (LOQs), with values of 1–5 µg/kg achieved for the target analytes in various matrices. Linearity was estimated from matrix-matched calibration curves constructed using six concentration levels ranging from 1- to 6-fold increases in the LOQs of each analyte, and the correlation coefficients (R2) were ≥0.9869. Recoveries (at three concentration levels of 1-, 2-, and 3-fold increases in the LOQ) of 73–104% were achieved with relative standard deviations (RSDs) ≤7.7% (intra-day and inter-day precision). Ten types of each matrix procured from large markets were evaluated, and all tested samples showed negative results. The current protocol is simple and versatile and can be used for routine detection of plant alkaloids in animal food products. [ABSTRACT FROM AUTHOR]

Pesticides, which are used as plant protection products, can enter the food chain, and exposure to these xenobiotics can cause a wide array of health problems in humans. Therefore, the objective of the present study was to develop an analytical method for the simultaneous determination of residual spinosad (sum of spinosyn A and D), temephos and piperonyl butoxide in porcine muscle, egg, milk, eel, flatfish and shrimp (sampling period: February to June 2018) using liquid chromatography–triple quadrupole tandem mass spectrometry (LC–MS/MS). The target analytes were extracted with a combination of acidified acetonitrile and ethyl acetate and subsequently purified with original QuEChERS kits (composed of magnesium sulfate and sodium chloride) as well as n‐hexane. All analytes were separated on a reversed‐phase analytical column using a mobile phase of (A) 0.1% formic acid containing 10 mm ammonium formate in distilled water and (B) methanol. Good linearity (R2 ≥ 0.980) was achieved over the tested concentration range (3.5–35 μg/kg for spinosyn A; 1.5–15 μg/kg for spinosyn D; 5–50 μg/kg for temephos and piperonyl butoxide) in matrix‐matched standard calibrations. Fortified samples at three spiking levels yielded recoveries in the range of 71–105% with relative standard deviations ≤9.2%. The applicability of the method was evaluated via evaluating samples collected from a large wholesale market located in Seoul, and none of the samples contained any of the target analytes. In conclusion, the current approach is simple, efficient and reliable and can successfully determine the residual levels of spinosad, temephos and piperonyl butoxide in complex animal‐derived food products. [ABSTRACT FROM AUTHOR]

A reliable and highly sensitive detection method based on liquid chromatography coupled with triple quadrupole electrospray tandem mass spectrometry (LC‐MS/MS) analysis has been developed for determination and quantification of halquinol, including 5,7‐dichloroquinolin‐8‐ol and 5‐chloroquinolin‐8‐ol. The target analytes were extracted from porcine muscle, egg, milk, eel, flatfish and shrimp using a mixture of acetonitrile and ethyl acetate followed by liquid–liquid purification with n‐hexane. The analytes were separated on an Agilent Eclipse XDB‐C18 reversed‐phase analytical column using 0.05% formic acid in distilled water and acetonitrile as mobile phases. Good linearity from six‐point matrix‐matched calibration was obtained with correlation coefficients (R2) ≥ 0.9904. Recoveries from three spiking levels (5, 10 and 20 μg/kg) ranged between 70.6 and 101.7% in various matrices with relative standard deviations ≤8.6%. Samples acquired from markets located in Seoul, Republic of Korea, tested negative for the target analytes. In conclusion, the proposed method is versatile and precise for the routine detection of halquinol residual levels in animal‐derived food products intended for human consumption. [ABSTRACT FROM AUTHOR]

A reliable and highly sensitive screening method based on liquid chromatography coupled with triple-quadrupole electrospray tandem mass spectrometry (LC-MS/MS) analysis has been developed for the detection and quantification of three veterinary drugs, including buparvaquone, nystatin, and etomidate impurity B CRS. The tested drugs were extracted from samples of porcine muscle, pasteurized whole milk, and eggs using 10 mM ammonium formate in acetonitrile followed by liquid-liquid purification with n -hexane. Chromatographic separation was achieved on a Phenomenex Luna C18 analytical column using 0.1% formic acid in ultrapure water (A) and acetonitrile (B) as mobile phases. All the matrix-matched calibration curves were linear ( R 2 ≥ 0.9756) over the concentration levels of the drugs tested. Recovery at two spiking levels (equivalent to the limit of quantification (LOQ) = 5 ng/g and 2 × LOQ) ranged from 72.88% to 92.59% with intra- and inter-day precisions <17%, except for porcine muscle spiked with 5 ng/g nystatin (RSD = 25.15%). Samples collected from markets located in Seoul, Republic of Korea, tested negative for all the drugs analyzed. In summary, this method is suitable for screening and quantifying the selected drugs in a single chromatographic run and with high selectivity in animal-derived food products meant for human consumption. [ABSTRACT FROM AUTHOR]

Herein, we developed a simple analytical procedure for the quantitation of bithionol residues in animal-derived food products such as porcine muscle, eggs, milk, eel, flatfish, and shrimp using a modified quick, easy, cheap, effective, rugged, and safe (QuEChERS) extraction method coupled with liquid chromatography–electrospray ionization tandem mass spectrometry (LC-ESI + /MS-MS). Samples were extracted with 0.1% solution of formic acid in acetonitrile and the extract was purified using a C18 sorbent. Separation was performed on a Waters XBridge™ C18 reversed-phase analytical column using 0.1% solution of formic acid/acetonitrile as the mobile phase. Six-point matrix-matched calibration indicated good linearity, with the calculated coefficients of determination ( R 2 ) being ≥ 0.9813. Intra- and inter-day recoveries (determined at spiking levels equivalent to 1 × and 2 × the limit of quantitation (0.25 μg/kg)) ranged between 80.0 and 94.0%, with the corresponding relative standard deviations (RSDs) being ≤ 8.2%. The developed experimental protocol was applied to different samples purchased from local markets in Seoul, which were tested negative for bithionol residues. In conclusion, the proposed method proved to be versatile and precise, being ideally suited for the routine detection of bithionol residues in animal-derived food products with various protein and fat contents. [ABSTRACT FROM AUTHOR]

A modified quick, easy, cheap, effective, rugged, and safe (QuEChERS) extraction method coupled with liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI + /MS-MS) was developed for quantification of fenobucarb residues in animal food products, such as porcine muscle, egg, and whole milk, and aquatic food products, such as eel, flatfish, and shrimp. Acetonitrile with the addition of 0.1% trifluoroacetic acid was employed as an extraction solvent and was compared with acetonitrile alone and 0.1% formic acid in acetonitrile. All extracted samples were purified using C18 sorbent. The best extraction efficiencies, expressed as recovery at two spiking levels equivalent to 1- and 2-times the limit of quantification (LOQ = 2 μg/kg) were achieved using 0.1% trifluoroacetic acid in acetonitrile and ranged from 61.38 to 102.21% in all matrices, with relative standard deviations (RSDs) < 13% (except for the low spiking of porcine muscle and the high spiking of whole milk, for which the RSDs were > 20%). Six-point matrix-matched calibration was used for quantification and the determination coefficients were good ( R 2 ≥ 0.9865). The method was verified by application to samples purchased from local markets and none of the samples tested positive. In conclusion, the developed method is simple and versatile and can be used for the routine detection of fenobucarb in different animal food products having varying protein and fat contents with satisfactory accuracy and precision. [ABSTRACT FROM AUTHOR]