Solid-phase extraction coupled with liquid chromatography-tandem mass spectrometry for determination of trace rosiglitazone in urine

This project evaluated solid-phase extraction (SPE) combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to determine the trace amount of rosiglitazone in human urine. The analytical performance of four modes of LC-MS and tandem MS operation (atmospheric pressure chemical ionization (APCI), electrospray ionization (ESI), positive and negative ionization) was compared for two mass spectrometers, a triple-quadrupole and a quadrupole ion trap instrument. Rosiglitazone was extracted from urine using a SPE cartridge of 50mg C8 sorbent and acetonitrile used as the eluting solvent. Samples were then separated on a RP18 column interfaced with a tandem mass spectrometer. The recovery of rosiglitazone was greater than 91.2%. The urine assay combining SPE and LC-APCI-MS/MS of triple-quadrupole was proved a very selective and sensitive method for determination of trace rosiglitazone. The assay was linear over a wide range, with a lower limit of quantification of 0.1 ng/mL using 1 mL of urine. The intra- and inter-day precisions were <9.8% and <7.9%, respectively, and the accuracies were in the range 91.0-103.6%. The rosiglitazone concentration profile in human urine was also determined. The results of this study reveal the adequacy of SPE-LC-APCI-MS/MS method for analyzing rosiglitazone from diabetic patients' urines. The concentrations of rosiglitazone were detected to range from 760 to 164 pg/mL.     

Development of a solid phase extraction protocol coupled with liquid chromatography mass spectrometry to analyze central carbon metabolites in lake sediment microcosms

An ion exchange solid phase extraction (SPE) strategy is developed for application with liquid chromatography-tandem quadrupole mass spectrometry (LC-MS/MS) for characterization of central carbon metabolites involved in methane assimilation and adjacent pathways in natural mixtures. For this purpose, short-time microcosm samples were obtained from lake sediment known to consume methane. Three SPE procedures were developed for the recovery of 51 targeted metabolites from five compound classes (amino acids, carboxylic acids, sugar phosphates, nucleotides and acyl-CoAs). The three SPE procedures employed were mixed mode (i) strong cation exchange, (ii) strong anion exchange and (iii) weak anion exchange. By spiking stable isotopic labeled standards, validation of the SPE procedures for the sediment extracts demonstrated that a 3 cm(3), 60 mg SPE sorbent bed provided effective loading capacity for targeted metabolites with an analytical variation of 16% RSD. We readily analyzed 32 of the targeted 51 metabolites using LC-MS/MS after sediment sample extraction, cleanup and pre-concentration. The remaining 19 targeted metabolites were either at, or below, the limit of detection. The current approach provides a good workflow for absolute quantification of intermediates in C(1)-carbon metabolism in natural microbial communities.     

Determination of multiresidue quinolones regulated by the European Union in pig liver samples. High-resolution time-of-flight mass spectrometry versus tandem mass spectrometry detection

The use of liquid chromatography coupled to orthogonal acceleration time-of-flight mass spectrometry (LC-ToF-MS) provides an attractive alternative to liquid chromatography coupled to quadrupole (LC-MS) or triple quadrupole mass spectrometry (LC-MS/MS) in multiresidue analysis. ToF-MS provides accurate mass information and a significantly higher mass resolution than quadrupole analyzers. In this work, the influential parameters in time-of-flight detection using an electrospray ionization (ESI) source were studied using a central composite design to obtain the main effects and their two-factor interactions. The method developed uses LC-ESI-ToF-MS to determine and characterize quinolones regulated by the EU in pig liver samples below the maximum residue limits (MRLs). Linearity, decision limit, detection capability, detection and quantification limits, precision and recoveries were determined and adequate results were obtained, with quantification limits between 1.5 and 6 microg kg(-1) and recoveries higher than 60% for all quinolones. Limits of detection are lower than 2 microg kg(-1). Results obtained using LC-ESI-ToF-MS were compared with those obtained using LC coupled to a quadrupole and to triple quadrupole mass spectrometer. The work described in this paper illustrates the suitability and excellent confirmatory potential of LC-ToF-MS for multiresidue analysis in food samples.     

Determination of faropenem in human plasma and urine by liquid chromatography-tandem mass spectrometry

A simple, rapid and sensitive liquid chromatography/electrospray tandem mass spectrometry (LC-MS/MS) quantitative detection method, using cefalexin as internal standard, was developed for the analysis of faropenem in human plasma and urine. After precipitation of the plasma proteins with acetonitrile, the analytes were separated on a C18 reversed-phase column with 0.1% formic acid-methanol (45:55, v/v) and detected by electrospray ionization mass spectrometry in positive multiple reaction monitoring mode. Calibration curves with good linearities (r=0.9991 for plasma sample and r=0.9993 for urine sample) were obtained in the range 5-4000 ng/mL for faropenem. The limit of detection was 5 ng/mL. Recoveries were around 90% for the extraction from human plasma, and good precision and accuracy were achieved. This method is feasible for the evaluation of pharmacokinetic profiles of faropenem in humans, and to our knowledge, it is the first time the pharmacokinetic of faropenem has been elucidated in vivo using LC-MS/MS.     

Quantification of 15-F2t-isoprostane in human plasma and urine: results from enzyme-linked immunoassay and liquid chromatography/tandem mass spectrometry cannot be compared

Quantification of F(2)-isoprostanes is considered a reliable index of the oxidative stress status in vivo. Several immunoassays and chromatography/mass spectrometry-based assays are available for 15-F(2t)-isoprostane quantification. However, it remains unclear if results of immunoassays using different assays can be compared with those of liquid chromatography/mass spectrometry (LC/MS) assays. Previous studies comparing enzyme-linked immunosorbent assay (ELISA) and more specific gas chromatography/mass spectrometry assays have already indicated that ELISAs may overestimate 15-F(2t)-isoprostane concentrations in human plasma. Concentrations of 15-F(2t)-isoprostane in 25 human plasma and urine samples were measured by three commercially available ELISA assays (Assay Designs, Cayman Chemical and Oxford Biomedical Research) and compared with the concentrations measured with a validated, semi-automated high-throughput HPLC tandem mass spectrometry assay (LC/LC-MS/MS). All three ELISAs measured substantially higher 15-F(2t)-isoprostane concentrations (2.1-182.2-fold higher in plasma; 0.4-61.9-fold higher in urine) than LC/LC-MS/MS. Utilization of solid-phase extraction (SPE) columns, especially isoprostane affinity purification columns, brought ELISA isoprostane urine concentrations closer to the LC/LC-MS/MS results. However, SPE did not have much of an effect on ELISA plasma concentrations which remained significantly higher than corresponding LC/LC-MS/MS results. A poor correlation not only between LC/LC-MS/MS and immunoassay results, but also among the immunoassays was found. Especially in plasma, ELISAs grossly overestimate 15-F(2t)-isoprostane concentrations and are not comparable with each other or with LC/LC-MS/MS. It is most disturbing that a sample with relatively high concentrations measured with one ELISA may show low concentrations with another ELISA, and vice versa, potentially affecting the conclusions drawn from such data. The use of specific mass spectrometry-based assays seems advisable.     

Design of online solid phase extraction-liquid chromatography-tandem mass spectrometry (SPE-LC-MS/MS) hyphenated systems for quantitative analysis of small organic compounds in biological matrices

Three online solid phase extraction-liquid chromatography-tandem mass spectrometry (SPE-LC-MS/MS) method examples are presented where two different types of chromatographic columns or solvent systems were coupled to meet specific analytical objectives: (i) SPE of target analytes by restricted access media from high ionic strength urine matrix was coupled with reversed phase LC-MS/MS conditions accommodating high ionization potentials of the analytes (urinary bisphenol A and other phenolic derivatives); (ii) strong cation exchange SPE of analytes of diverse polarity and pK(a) was coupled with reversed phase LC-MS/MS analysis (urinary atrazine metabolites); (iii) pre-concentration of low pg per sample analytes by weak anion exchange SPE was hyphenated with ion pair LC-MS analysis (intracellular nucleotide triphosphate analogs). With these examples we suggest a conductive generic work flow for the development of online SPE-LC-MS methods and show how advanced commercial LC devices and software allow for the design of complex yet highly versatile analytical separation systems suited to the unique physicochemical properties of the target analytes.     

Identification of phenyl-N-methylcarbamates and their transformation products in Tunisian surface water by solid-phase extraction liquid chromatography-tandem mass spectrometry

Liquid chromatography-pneumatically assisted electrospray mass spectrometry with both negative and positive ionization has been used for the determination of carbamates pesticides and their transformation products in Tunisian surface water. Eight pesticides and four of their hydrolysis products were covered in this study.Optimization of electrospray inlet conditions is described as well as results from investigations of the linearity of the detector response. Conditions for tandem mass spectrometry (MS-MS) detection of characteristic daughter ions formed by collision induced dissociation (CID) of the parent ion are described. Detection limits using MS in the selected ion monitoring (SIM) mode were generally in the order of 0.5 μg L⁻¹ or below. A principle of analysis is proposed based on triple quadrupole MS as a method for quantitative determination followed by verification of positive findings by CID-MS-MS. Application of the method for detecting carbamates residues in surface water is demonstrated.     

Analysis of polyamines as carbamoyl derivatives in urine and serum by liquid chromatography-tandem mass spectrometry

A quantitative analysis of polyamines in urine and serum by liquid chromatography-tandem mass spectrometry (LC-MS/MS) is described. The polyamines were carbamylated with isobutyl chloroformate, extracted with diethyl ether under pH 9.0, and analyzed by LC-MS/MS with single reaction monitoring mode. The limit of quantification was 1 ng/mL based on a signal-to-noise ratio>3, and the correlation coefficient (r2) for the calibration curves was >0.99 for both urine and serum samples. The present method was applied to urine and serum samples from 30 breast cancer patients and 30 normal female controls. There was no significant difference in the urinary polyamine levels between breast cancer patients and controls. However, 1,3-diaminopropane, putrescine, spermine and N-acetylspermidine levels in serum increased in breast cancer patients. These four serum polyamines may be a good index to study both production and metabolism of polyamines, and a useful tool in assessment of the polyamine status of breast cancer patients.     

Strategies for the elimination of matrix effects in the liquid chromatography tandem mass spectrometry analysis of the lipophilic toxins okadaic acid and azaspiracid-1 in molluscan shellfish

Considerable efforts are being made worldwide to replace in vivo assays with instrumental methods of analysis for the monitoring of marine biotoxins in shellfish. Analysis of these compounds by the preferred technique of liquid chromatography tandem mass spectrometry (LC-MS/MS) is challenged by matrix effects associated with the shellfish tissues. In methods validation, assessment of matrix interferences is imperative to ensure the validity and accuracy of results being produced. Matrix interferences for the analysis of okadaic acid (OA) and azaspiracid 1 (AZA1) were assessed using acidic methods on electrospray triple stage quadrupole (TSQ) and hybrid quadrupole time of flight (QToF) instruments by the use of matrix matched standards for different tissue types. Using an acidic method no matrix interference and suppression was observed on the TSQ for OA and AZA1 respectively, whilst the opposite was observed on the QToF; matrix enhancement for OA and no matrix interference for AZA1. The suppression of AZAs on the TSQ was found to be due to interfering compounds being carried over from previous injections. The degree of suppression is very much dependant on the tissue type ranging from 15 to 70%. Several strategies were evaluated to eliminate these interferences, including the partitioning of the extract with hexane, optimisation of the chromatographic method and the use of on-line SPE. Hexane clean up did not have any impact on matrix effects. The use of an alkaline method and a modified acidic method eliminated matrix suppression for AZA1 on the TSQ instrument while an on-line SPE method proved to be effective for matrix enhancement of OA on the QToF.     

Stereoselective separation and determination of triadimefon and triadimenol in wheat, straw, and soil by liquid chromatography-tandem mass spectrometry

A sensitive and rapid analytical method was developed for simultaneous determination of triadimefon (TF) and triadimenol (TN) stereoisomers in wheat, straw, and soil by liquid chromatography coupled with triple quadrupole mass spectrometry (LC-MS/MS). The direct enantioseparation of TF and TN was performed on a Lux cellulose-1 column packed with cellulose-tris-(3,5-dimethylphenylcarbamate). The effects of mobile-phase composition on the separation were investigated and stereoisomeric elution orders were confirmed with a polarimeter detector. The pesticides were extracted from samples with acetonitrile and cleaned up by solid-phase extraction or activated carbon. Based on the developed stereoselective LC-MS/MS method, for TF and TN stereoisomers, good linearities were obtained over the concentration range of 0.003-4 mg/L; recoveries were 84.2-102.7% in wheat, 84.0-104.0% in straw, and 85.2-106.8% in soil at spiked concentrations of 0.007-2.0 mg/kg; intra-day and inter-day assay precisions were below 12.2%. Limits of detection (LODs) and limits of quantification (LOQs) in wheat, straw, and soil were 0.001-0.005 mg/kg and 0.007-0.02 mg/kg, respectively. Finally, the method was successfully applied to detect TF and TN stereoisomers in wheat, straw, and soil samples from residual trials in farm.     

Combined use of liquid chromatography triple quadrupole mass spectrometry and liquid chromatography quadrupole time-of-flight mass spectrometry in systematic screening of pesticides and other contaminants in water samples

As a suitable way for routine screening of pesticides and control of other organic contaminants in water, the combination of liquid chromatography triple quadrupole tandem mass spectrometry (LC–QqQ-MS/MS) and liquid chromatography–hybrid quadrupole time-of-flight mass spectrometry (LC–QTOF-MS) has been applied to the analysis of 63 surface and waste water samples after conventional solid-phase extraction (SPE). The extracts were screened for 43 pesticides or degradation products by LC–QqQ-MS/MS achieving limits of detection (LOD) ranged from 0.04 to 2 ng L⁻¹. Of the 43 selected pesticides, 33 were detected in water samples. The ESI–QTOF MS instrument was run using two simultaneous acquisition functions with low and high collision energy (MS^E approach) and acquiring the full mass spectra. A home-made database containing more than 1100 organic pollutants was used for substance identification. Around 250 of these compounds were available at the laboratory as reference standards. Five pesticides and 3 of their degradation products, different to those selected in the QqQ method, were detected by QqTOF-MS. Thirteen pharmaceuticals and two drugs of abuse were also identified in the samples. In practice, the sample preparation proved to be suitable for both techniques and for a wide variety of substances with different polarity. Mutual confirmation and evidence of co-occurrence of several other organic contaminants were the main advantages of the combination of both techniques.     

Elucidation of urinary metabolites of fluoxymesterone by liquid chromatography-tandem mass spectrometry and gas chromatography-mass spectrometry

The suitability of liquid chromatography tandem mass spectrometry (LC-MS/MS) and gas chromatography mass spectrometry (GC-MS) for the elucidation of fluoxymesterone metabolism has been evaluated. Electrospray ionization (ESI) and collision induced dissociation (CID) fragmentation in LC-MS/MS and electron impact spectra (EI) in GC-MS have been studied for fluoxymesterone and two commercially available metabolites. MS(n) experiments and accurate mass measurements performed by an ion-trap analyser and a QTOF instrument respectively have been used for the elucidation of the fragmentation pathway. The neutral loss scan of 20 Da (loss of HF) in LC-MS/MS has been applied for the selective detection of fluoxymesterone metabolites. In a positive fluoxymesterone doping control sample, 9 different analytes have been detected including the parent compound. Seven of these metabolites were also confirmed by GC-MS including 5 previously unreported metabolites. On the basis of the ionization, the CID fragmentation, the accurate mass of the product ions and the EI spectra of these analytes, a tentative elucidation as well as a proposal for the metabolic pathway of fluoxymesterone has been suggested. The presence of these compounds has also been confirmed by the analysis of five other positive fluoxymesterone urine samples.     

Rapid determination of quinolones in cosmetic products by ultra high performance liquid chromatography with tandem mass spectrometry

This study developed an improved analytical method for the simultaneous quantification of 13 quinolones in cosmetics by ultra high performance liquid chromatography combined with ESI triple quadrupole MS/MS under the multiple reaction monitoring mode. The analytes were extracted and purified by using an SPE cartridge. The limits of quantification ranged from 0.03 to 3.02 μg/kg. The precision for determining the quinolones was <19.39%. The proposed method was successfully developed for the determination of quinolones in real cosmetic samples.     

Characterization and identification of pradimicin analogs from Actinomadura hibisca using liquid chromatography-tandem mass spectrometry

Microbial cultures produce complex and potentially interesting mixtures of biosynthetic intermediates and derivatives of metabolites. These mixtures' reliable identification is important and so too is the development of techniques for their analysis. Here, a simple and highly selective method of detecting the biosynthetic congeners involved in the pentangular polyphenol pradimicin (PR) pathway from Actinomadura hibisca fermentation was developed. Solid-phase extraction (SPE) cleanup using an OASIS HLB cartridge was a simple and reliable tool for the extraction of PRs from a fermentation broth. The separation of each natural PR analog--eluted with a gradient system of aqueous acetonitrile through a reversed-phase C(18) column containing ammonium acetate and acetic acid as additives--allowed their simultaneous profiling. The combined use of SPE cleanup and chromatographic separation, coupled with electrospray ionization-tandem mass spectrometry (ESI-MS/MS) detection was demonstrated to be sufficiently accurate and reliable to analyze the natural PR analogs produced from A. hibisca. Ten natural PRs were identified: four alanine-containing (PRA, PRC, PRL, and PRB), two glycine-substituted (PRD and PRE), and four serine-substituted (PRFA-1, PRFA-2, PRFL, and PRFB). This report demonstrates the first use of both SPE cleanup and HPLC-ESI-MS/MS to profile a wide range of structurally closely related PRs in a bacterial fermentation broth.     

Liquid chromatography-tandem mass spectrometry for the identification of L-tetrahydropalmatine metabolites in Penicillium janthinellum and rats

L-tetrahydropalmatine (L-THP) is an active alkaloid from Stephania ainiaca Diels. In order to compare the similarities and differences of microbial and mammalian metabolisms of L-THP, the microbial transformation by Penicillium janthinellum and metabolism in rats were investigated. Biotransformation of L-THP by Penicillium janthinellum AS 3.510 resulted in the formation of three metabolites. Their structures were identified as L-corydalmine, L-corypalmine and 9-O-desmethyl-L-THP, respectively, by comprehensive nuclear magnetic resonance and mass spectrometry (MS) analysis. Six metabolites (M1-M6) were detected from the in vivo study in rats and three of which (L-corydalmine, L-corypalmine and 9-O-desmethyl-L-THP) were identified as the same compounds as those obtained from microbial metabolism by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis and comparison with reference standards obtained from microbial metabolism. The structures of the additional three metabolites were tentatively deduced as 2-O-desmethyl-L-THP and two di-O-demethylated L-THP by LC-MS/MS analysis. Time courses of microbial and rat metabolisms of L-THP were also investigated.     

Synthesis of benzofurazan derivatization reagents for carboxylic acids in liquid chromatography/electrospray ionization-tandem mass spectrometry

The applicability of benzofurazan derivatization regents to carboxylic acids analysis in LC/ESI-MS/MS (high-performance liquid chromatography/electrospray ionization tandem mass spectrometry) was examined. The product ion spectra of DAABD-AE {4-[2-(N,N-dimethylamino)ethylaminosulfonyl]-7-(2-aminoethylamino)-2,1,3-benzoxadiazole}, DAABD-PZ {4-[2-(N,N-dimethylamino)ethylaminosulfonyl]-7-N-piperazino-2,1,3-benzoxadiazole}, DAABD-PiCZ {4-[4-carbazoylpiperidin-1-yl]-7-[2-(N,N-dimethylamino)ethylaminosulfonyl]-2,1,3-benzoxadiazole}, DAABD-ProCZ {4-[2-carbazoylpyrrolidin-1-yl]-7-[2-(N,N-dimethylamino) ethylaminosulfonyl]-2,1,3-benzoxadiazole} and DAABD-Apy {4-[2-(N,N-dimethylamino)ethylaminosulfonyl]-7-(3-aminopyrrolidin-1-yl)-2,1,3-benzoxadiazole}, and their acetylated compounds were obtained. An intense fragment ion at m/z 151 corresponding to (dimethylamino)ethylaminosulfonyl moiety was observed in each spectra, suggesting that these reagents were suitable for ESI-MS/MS analysis. DAABD-AE, DAABD-APy and DAABD-PZ were applied to the analysis of octanoic acid and it was found that DAABD-AE and DAABD-APy gave high signal intensity suitable for LC/ESI-MS/MS.     

Determination of two oxy-pyrimidine metabolites of diazinon in urine by gas chromatography/mass selective detection and liquid chromatography/electrospray ionization/mass spectrometry/mass spectrometry

An analytical method was developed for the determination in urine of 2 metabolites of diazinon: 6-methyl-2-(1-methylethyl)-4(1H)-pyrimidinone (G-27550) and 2-(1-hydroxy-1-methylethyl)-6-methyl-4(1H)-pyrimidinone (GS-31144). Two of the urine sample preparation procedures presented rely on gas chromatography/mass selective detection (GC/MSD) in the selected ion monitoring mode for determination of G-27550. For fast sample preparation and a limit of quantitation (LOQ) of 1.0 ppb, urine samples were purified by using ENV+ solid-phase extraction (SPE) columns. For analyte confirmation at an LOQ of 0.50 ppb, classical liquid/liquid partitioning was used before further purification in a silica SPE column. An SPE sample preparation procedure and liquid chromatography/electrospray ionization/mass spectrometry/mass spectrometry (LC/ESI/MS/MS) were used for both G-27550 and GS-31144. The limit of detection was 0.01 ng for G-27550 with GC/MSD, and 0.016 ng when LC/ESI/MS/MS was used for both G-27550 and GS-31144. The LOQ was 0.50 ppb for G-27550 when GC/MSD and the partitioning/SPE sample preparation procedure were used, and 1.0 ppb for the SPE only sample preparation procedure. The LOQ was 1.0 ppb for both analytes when LC/ESI/MS/MS was used.     

超高效液相色谱-四极杆串联飞行时间质谱分析黄酮类化合物及小毛茛茎叶的成分

为了探索液相色谱-质谱联用(LC-MS)技术在快速识别中药及天然产物成分中的应用,以黄酮对照品为研究前体,药用植物小毛茛为研究对象,采用超高效液相色谱/二极管阵列检测器-电喷雾四极杆串联飞行时间质谱(UPLC/DAD-ESI/Q-TOF MS)分析了黄酮类化合物同系物及同分异构体的色谱、质谱特性。结果显示:黄酮氧苷和黄酮碳苷的紫外吸收光谱及二级质谱具有显著性差异,糖苷化位置同保留时间、二级质谱碎片及相对丰度具有相关性。将该方法应用于小毛茛茎叶醇提液的分析,结合其酸水解液的分析,解析了22个黄酮醇糖苷和3个苷元。方法简便,具有可操作性。     

超高效液相色谱-三重四极杆质谱联用方法测定血浆和尿液中的α-龙葵碱、α-卡茄碱和茄啶

建立了超高效液相色谱-三重四极杆质谱联用方法,检测血浆和尿液中的α-龙葵碱、α-卡茄碱和茄啶。样品经2%(v/v,下同)甲酸水溶液等量稀释,再经混合型阳离子交换固相萃取柱(MCX SPE)净化,以0.1%甲酸乙腈溶液和含0.05%甲酸的5 mmol/L乙酸铵水溶液作为流动相进行梯度洗脱,在UPLC BEH C18色谱柱上实现分离,正离子电喷雾串联质谱多反应监测(ESI-MS/MS MRM)方式检测,基质匹配外标法定量。一次进样分析时间为5.5min。血浆和尿液中3种待测物的线性范围均为0.3~100 ng/mL,相关系数为0.997~0.999;样品的检出限为0.1 ng/mL,定量限为0.3 ng/mL;血浆和尿液中的平均加标回收率分别为82%~112%和96%~114%,相对标准偏差为4.0%~16%和2.7%~17%(n=6)。方法简单、准确、灵敏,适用于马铃薯中毒检测。     

Imitation of drug metabolism in cell co-culture microcapsule model using a microfluidic chip platform coupled to mass spectrometry

In this work,a multi-functional analysis platform by coupling a microfluidic chip to a mass spectrometry(MS) detector was described.We constructed a three-dimensional tumor-endothelial co-culture model for simulating drug resistance during tumor treatment.On this specially designed integrated platform,the first step was to prepare heterogeneous cell-encapsulated alginate microcapsules for threedimensional co-culture,and the second step was to achieve on-line perfusion culture and continuous drug stimulation on chip.It facilitates cell proliferation analysis and the collection of metabolism medium.After micro solid phase extraction column(SPE) pretreatment,subsequent mass spectrometry could detect drug metabolism.The high activity of two kinds of cells(A549 and HUVEC) shows the biocompatibility of the platform.Paclitaxel was used as a model drug,the distinctions of drug absorption between the mono-culture group and co-culture group were clearly observed by electrospray ionization quadrupole time-of-flight mass spectrometry(ESI-Q-TOF MS).Therefore,the integrated platform has shown promise as a high throughput,low cost for cell metabolism research and drug screening processes.