Multiple-stage mass spectrometry analysis of bisphenol A diglycidyl ether, bisphenol F diglycidyl ether and their derivatives

The fragmentation of bisphenol A diglycidyl ether (BADGE), bisphenol F diglycidyl ether (BFDGE) and their derivatives was studied by electrospray ionization tandem mass spectrometry. Multiple-stage mass spectrometry and accurate mass measurements were combined to establish the fragmentation pathways. BADGEs and BFDGEs tend to form ammonium adducts under electrospray conditions which fragmented easily. The fragmentation of [M+NH(4)](+) for BADGEs started with the cleavage of the phenyl-alkyl bond, which was followed by the α-cleavage of the ether group to generate the characteristic product ions at m/z 135, [C(9)H(11)O](+), and m/z 107, [C(7)H(7)O](+). The fragmentation of the BFDGE isomer mixtures was studied by on-line reversed-phase liquid chromatography coupled to multiple-stage mass spectrometry (LC/MS(n)). Information obtained from product ion spectra for each BFDGE isomer and its comparison with the fragmentation pathway of BADGE allowed each isomer and the chromatographic elution order to be identified.     

高效液相色谱-串联质谱法同时测定肉类罐头中双酚-二缩水甘油醚

建立了同时测定肉类罐头中双酚A-二缩水甘油醚(BADGE)、双酚F-二缩水甘油醚(BFDGE)及其衍生物双酚A-(2,3-二羟丙基)甘油醚(BADGE•H2O)、双酚A-双(2,3-二羟丙基)醚(BADGE•2H2O)、双酚A-(3-氯-2-羟丙基)(2,3-二羟丙基)醚(BADGE•H2O•HCl)、双酚A-(3-氯-2-羟丙基)甘油醚(BADGE•HCl)、双酚A-双(3-氯-2-羟丙基)醚(BADGE•2HCl)、双酚F-双(2,3-二羟丙基)醚(BFDGE•2H2O)、双酚F-双(3-氯-2-羟丙基)醚(BFDGE•2HCl)9种环境激素的高效液相色谱-串联质谱分析方法。样品经叔丁基甲醚提取,HLB固相萃取小柱净化,C18色谱柱分离,用5 mmol/L醋酸铵溶液(含0.1%甲酸)与甲醇为流动相梯度洗脱,质谱多反应监测(MRM)模式检测,基质标准校正,外标法定量。结果表明,这9种化合物在10.0～2000.0 μg/L范围内线性关系良好;定量限(以信噪比≥10计)为10.0 μg/kg;在高、中、低3个加标水平下9种化合物的平均添加回收率为79.6%～100.9%,相对标准偏差为6.3%～12.1%。该方法具有较高的灵敏度和准确度,能满足法规要求的对肉类罐头中双酚A-二缩水甘油醚、双酚F-二缩水甘油醚及其衍生物残留量的快速检测及准确定量。     

固相萃取-高效液相色谱-串联质谱测定水中8种双酚-二环氧甘油醚

建立了水中8种双酚-二环氧甘油醚（双酚A二缩水甘油醚（BADGE）及其衍生物双酚A（3-氯-2-羟丙基）甘油醚（BADGE·5HCl）、双酚A双（3-氯-2-羟丙基）醚（BADGE·52HCl）、双酚A（2,3-二羟丙基）甘油醚（BADGE·5H₂O）、双酚A双（2,3-二羟丙基）醚（BADGE·52H₂O）、双酚A（3-氯-2-羟丙基）（2,3-二羟丙基）醚（BADGE·5HCl·5H₂O）和双酚F-二环氧甘油醚（BFDGE）及其衍生物双酚F双（3-氯-2-羟丙基）醚（BFDGE·52HCl））的固相萃取-高效液相色谱-串联质谱（SPE-HPLC-MS/MS）测定方法。10个饮用水接触涂料样品在室温避光条件下,以超纯水浸泡（24±1）h,然后取200 mL经C₁₈固相萃取柱进行净化浓缩,以C₁₈色谱柱进行分离,以5 mmol/L醋酸铵、甲醇和水为流动相进行梯度洗脱,质谱多反应监测（MRM）模式检测,外标法定量。结果表明,8种双酚-二环氧甘油醚在0.007~5.00 μg/L线性关系良好,相关系数均大于0.9990,该方法对8种双酚-二环氧甘油醚的定量限为7~91 ng/L,回收率为79.1%~101%,RSD为4.0%~12%。该方法具有灵敏度高、选择性强的特点,能够满足水中双酚-二环氧甘油醚的快速检测和准确定量。     

多壁碳纳米管固相萃取-高效液相色谱-串联质谱法测定食品接触材料中双酚-二环氧甘油醚的迁移量

建立了测定食品接触材料中6种双酚-二环氧甘油醚(双酚A二缩水甘油醚(BADGE)及其衍生物双酚A(2,3-二羟丙基)甘油醚(BADGE•H2O)、双酚A(3-氯-2-羟丙基)甘油醚(BADGE•HCl)、双酚A(3-氯-2-羟丙基)(2,3-二羟丙基)醚(BADGE•H2O•HCl)和双酚F二缩水甘油醚(BFDGE)及其衍生物双酚F双(3-氯-2-羟丙基)甘油醚(BFDGE•2HCl))迁移到食品中的迁移量的高效液相色谱-串联质谱法(HPLC-MS/MS)。样品以叔丁基甲醚(MTBE)为提取溶剂,超声提取,提取液经多壁碳纳米管(MWCNTs)固相萃取(SPE)柱富集、净化。以COSMOSIL C18为分析柱,流动相为0.1%甲酸的5 mmol/L醋酸铵溶液和甲醇。6种双酚-二环氧甘油醚在1.0～100 μg/L范围内线性关系良好(r2＞0.9991)。在3个添加水平下,6种目标化合物的回收率范围为78.6%～89.9%,相对标准偏差小于10%。方法检出限范围为0.5～1.5 μg/L。该方法操作简单,灵敏度高,可应用于食品接触材料中双酚-二环氧甘油醚迁移量的快速检测。     

Fast liquid chromatography-tandem mass spectrometry for the analysis of bisphenol A-diglycidyl ether, bisphenol F-diglycidyl ether and their derivatives in canned food and beverages

In this work a fast liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS) method using a C18 Fused Core™ column, was developed for the simultaneous analysis of bisphenol A diglycidyl ether (BADGE), bisphenol A (2,3-dihydroxypropyl) glycidyl ether (BADGE·H₂O), bisphenol A bis(2,3-dihydroxypropyl) ether (BADGE·2H₂O), bisphenol A (3-chloro-2-hydroxypropyl) glycidyl ether (BADGE·HCl), bisphenol A bis(3-chloro-2-hydroxypropyl) ether (BADGE·2HCl) and bisphenol A (3-chloro-2-hydroxypropyl)(2,3-dihydroxypropyl ether) (BADGE·HCl·H₂O) and bisphenol F diglycidyl ether (BFDGE), bisphenol F bis(2,3-dihydroxypropyl) ether (BFDGE·2H₂O), bisphenol F bis(3-chloro-2-hydroxypropyl) ether (BFDGE·2HCl). The LC method was coupled with a triple quadrupole mass spectrometer, using an ESI source in positive mode and using the [M+NH₄]⁺ adduct as precursor ion for tandem mass spectrometry experiments. The method developed was applied to the determination of these compounds in canned soft drinks and canned food. OASIS HLB solid phase extraction (SPE) cartridges were used for the analysis of soft drinks, while solid canned food was extracted with ethyl acetate. Method limits of quantitation ranged from 0.13 μg L⁻¹ to 1.6 μg L⁻¹ in soft drinks and 1.0 μg kg⁻¹ to 4.0 μg kg⁻¹ in food samples. BADGE·2H₂O was detected in all the analyzed samples, while other BADGEs such as BADGE·H₂O, BADGE·HCl·H₂O, BADGE·HCl and BADGE·2HCl were also detected in canned foods.     

QuEChERS法结合高效液相色谱-串联质谱法测定保健食品中12种双酚类化合物

建立了采用高效液相色谱-串联质谱(HPLC-MS/MS)同时测定粉剂、片剂和胶囊剂等保健食品中12种双酚类化合物的检测方法。样品中双酚类化合物经1%(v/v)乙酸乙腈溶液提取,QuEChERS方法净化;12种化合物经Thermo Aquasil C₁₈色谱柱(150 mm×4.6 mm,3.0 μm)分离后,分别在串联质谱正、负离子多反应监测(MRM)模式下检测,基质匹配外标法定量。研究结果表明,在0.5~50.0 μg/kg内,12种双酚类化合物的线性相关系数均大于0.99,方法的检出限(S/N>3)为0.1~0.5 μg/kg,定量限(S/N>10)为0.4~1.7 μg/kg,不同基质的保健食品在3个添加水平(2.0、5.0和10.0 μg/kg)下的回收率为60.5%~116.3%(n=6),相对标准偏差(RSD)为6.8%~11.2%(n=6)。方法操作简单、耗时短、灵敏度高,满足现行法规要求,可实现保健食品中双酚类化合物的定性和定量测定。     

Determination of bisphenol diglycidyl ether residues in canned foods by pressurized liquid extraction and liquid chromatography-tandem mass spectrometry

A new confirmatory method for simultaneous determination of bisphenol diglycidyl ether residues (BADGE, BADGE.H(2)O, BADGE.2H(2)O, BADGE.H(2)O.HCl, BADGE.HCl, BADGE.2HCl, BFDGE and BFDGE.2HCl) from canned food has been developed. The proposed method includes extraction by pressurized liquid extraction (PLE) followed by liquid-liquid partition and purification by solid phase extraction (SPE). Several solvent systems and different operating conditions (time, temperature) have been investigated for PLE optimization. A reversed-phase high-performance liquid chromatography (RP-HPLC) coupled to atmospheric pressure chemical ionisation tandem mass spectrometry (APCI-MS-MS) method was developed for the separation, quantification and confirmation. The ion source settings were optimized using a design of experiments (DOE). The optimized method was applied to the determination of these chemicals at very low levels in different samples with a quantification limit of 5 ng/g. Recoveries ranged between 82 and 101% and standard deviations were less than 10%.     

Quantification of derivatives of bisphenol A diglycidyl ether (BADGE) and novolac glycidyl ether (NOGE) migrated from can coatings into tuna by HPLC/fluorescence and MS detection

A reversed phase high performance liquid chromatographic method combined with fluorescence and mass spectrometric detection in series is presented for the separation and quantification of bisphenol A diglycidyl ether (BADGE) and novolac glycidyl ether (NOGE) derivatives in extracts from food can coatings, tuna and oil. Fifteen samples of tuna cans bought in four European countries were investigated. Atmospheric pressure chemical ionization mass spectrometry in the positive ion mode (APCI(+)-MS) allowed to tentatively identify BADGE and NOGE related compounds originating from reactions of the glycidyl ethers with bisphenols, phenol, butanol, water and hydrochloric acid. Quantification was based on the external standard method and fluorescence detection. Mass fractions up to 3.7 micrograms/g were found for hydrochlorination products of bisphenol F diglycidyl ether (BFDGE + 2HCl) in tuna. Furthermore, total migration quantities of phenolic ether compounds were estimated. The highest values found were 20 micrograms/g in tuna and 43 micrograms/g in the oil phase.     

Microwave‐assisted extraction for the simultaneous determination of Novolac glycidyl ethers,bisphenol A diglycidyl ether,and its derivatives in canned food using HPLC with fluorescence detection

A microwave‐assisted extraction (MAE) protocol and an efficient HPLC analysis method were first developed for the fast extraction and simultaneous determination of bisphenol F diglycidyl ether (Novolac glycidyl ether 2‐Ring), Novolac glycidyl ether 3‐Ring, Novolac glycidyl ether 4‐Ring, Novolac glycidyl ether 5‐Ring, Novolac glycidyl ether 6‐Ring, bisphenol A diglycidyl ether, bisphenol A (2,3‐dihydroxypropyl) glycidyl ether, bisphenol A (3‐chloro‐2‐hydroxypropyl) glycidyl ether, bisphenol A bis(3‐chloro‐2‐hydroxypropyl) ether, bisphenol A (3‐chloro‐2‐hydroxypropyl) (2,3‐dihydroxypropyl) ether in canned fish and meat. After being optimized in terms of solvents, microwave power and irradiation time, MAE was selected to carry out the extraction of ten target compounds. Analytes were purified by poly(styrene‐co‐divinylbenzene) SPE columns and determinated by HPLC‐fluorescence detection. LOD varied from 0.79 to 3.77 ng/g for different target compounds based on S/N=3; LOQ were from 2.75 to 10.92 ng/g; the RSD for repeatability were <8.64%. The analytical recoveries ranged from 70.46 to 103.44%. This proposed method was successfully applied to 16 canned fish and meat, and the results acquired were in good accordance with the studies reported. Compared with the conventional liquid–liquid extraction and ultrasonic extraction, the optimized MAE approach gained the higher extraction efficiency (20–50% improved).     

高效液相色谱-串联质谱法检测婴幼儿血清中4种双酚类环境激素残留

目前,双酚类化合物是重要的工业原料,常用来制造塑料(奶)瓶、幼儿用吸口杯、食品和饮料(奶粉)罐内侧涂层,其具有类似雌激素的作用,摄入低剂量的双酚类物质便会引起机体尤其婴幼儿体内激素水平的调节。建立了一种同时测定婴幼儿血清中双酚A(BPA)、双酚B(BPB)、双酚F(BPF)、双酚S (BPS)4种双酚类环境激素的高效液相色谱-串联质谱法(HPLC-MS/MS)。以甲基叔丁基醚(MTBE)为提取溶剂,采用液液萃取的方法进行样品处理,同时对影响4种双酚类环境激素提取效率的提取溶剂、提取时间、提取溶剂体积等影响因素进行了优化。100 μL血清样本在40 ℃下经400 μL MTBE提取15 min后,采用Waters ACQUITY UPLC BEH C18柱(50 mm×2.1 mm, 1.7 μm)进行分离,以超纯水和含0.5 mmol/L乙酸铵的甲醇溶液为流动相进行梯度洗脱,流速为0.2 mL/min,采用电喷雾电离、负离子模式扫描,在多反应监测(MRM)模式下测定。BPA、BPB、BPS在0.25~100 μg/L范围内线性关系良好,BPF在1~00 μg/L范围内线性关系良好,相关系数为0.9929~0.9959;方法的检出限分别为0.05、0.05、0.05、0.5 μg/L;在3个添加水平(5、20、100 μg/L)下,4种目标化合物的回收率为84.56%~104.43%,相对标准偏差小于10%。应用该方法对150例婴幼儿血清样品进行检测,结果表明:BPA、BPF、BPS在男童和女童血清中的检出率分别为90.67%和89.33%、6.67%和1.33%、5.33%和16.00%, BPB未被检出。该方法操作简单,回收率好,精密度高,适用于婴幼儿血清中4种双酚类环境激素的同时测定。     

Quantification of derivatives of bisphenol A diglycidyl ether (BADGE) and novolac glycidyl ether (NOGE) migrated from can coatings into tuna by HPLC/fluorescence and MS detection

A reversed phase high performance liquid chromatographic method combined with fluorescence and mass spectrometric detection in series is presented for the separation and quantification of bisphenol A diglycidyl ether (BADGE) and novolac glycidyl ether (NOGE) derivatives in extracts from food can coatings, tuna and oil. Fifteen samples of tuna cans bought in four European countries were investigated. Atmospheric pressure chemical ionization mass spectrometry in the positive ion mode (APCI(+)-MS) allowed to tentatively identify BADGE and NOGE related compounds originating from reactions of the glycidyl ethers with bisphenols, phenol, butanol, water and hydrochloric acid. Quantification was based on the external standard method and fluorescence detection. Mass fractions up to 3.7 μg/g were found for hydrochlorination products of bisphenol F diglycidyl ether (BFDGE + 2HCl) in tuna. Furthermore, total migration quantities of phenolic ether compounds were estimated. The highest values found were 20 μg/g in tuna and 43 μg/g in the oil phase. Received: 16 October 2000 / Accepted: 17 November 2000     

Accurate mass and nuclear magnetic resonance identification of bisphenolic can coating migrants and their interference with liquid chromatography/tandem mass spectrometric analysis of bisphenol A

Two unknown compounds were previously determined to be potential interferences in liquid chromatography/tandem mass spectrometry (LC/MS/MS) analysis of bisphenol A (BPA) in canned infant formula. Both yielded two identical MS/MS transitions to BPA. The identities of the unknowns were investigated using accurate mass LC/MS, LC/MS/MS, and elemental formula and structures proposed. Exact identities were confirmed through purification or synthesis followed by (1)H and (13)C nuclear magnetic resonance (NMR) experiments, as well as comparisons of one unknown with commercial standards. Comparisons of negative ion electrospray ionization (ESI) MS/MS and accurate mass spectra suggested both unknowns to be structurally identical (to BPA and each other). Positive ion ESI spectra confirmed both were larger molecules, suggesting that in the negative mode they likely fragmented to the deprotonated BPA ion in the source [corrected]. Elemental composition of positive ion accurate mass spectra and NMR analysis concluded the unknowns were oxidized forms of the known epoxy can coating monomer, bisphenol A diglycidyl ether (BADGE). One of the unknowns, 2,2-[bis-4-(2,3-dihydroxypropoxy)phenyl]propane, commonly known as BADGE*2H(2)O, is widely reported as an epoxy-phenolic can coating migrant, but has not been suggested to interfere with the MS/MS analysis of BPA. The other unknown, 2-[4-(2,3-dihydroxypropoxy)phenyl]-2-[4'-hydroxyphenyl]propane, or the oxidized form of bisphenol A monoglycidyl ether (BAMGE*H(2)O), has not been previously reported in food or packaging.     

Determination of bisphenol A diglycidyl ether and its hydrolysis and chlorohydroxy derivatives by liquid chromatography-mass spectrometry

European Legislation establishes that the sum of the migration levels of bisphenol A diglycidyl ether (BADGE), its hydrolysis (BADGE.H2O and BADGE.2H2O) and chlorohydroxy (BADGE.HCl, BADGE.2HCl and BADGE.H2O.HCl) derivatives shall not exceed the limit of 1 mg/kg in foodstuffs or food simulants. A reversed-phase high-performance liquid chromatographic (RP-HPLC) method combined with mass spectrometry detection using atmospheric pressure chemical ionisation (APCI) is developed for the separation, quantification and identification of the interesting compounds. Quantification of the analytes was carried out in the single ion recording mode, once their characteristic masses were selected from their full spectra, by using an external calibration. The optimised method was suitable for the migration evaluation of these compounds in different samples.     

Identification of derivatives of bisphenol A diglycidyl ether and novolac glycidyl ether in can coatings by liquid chromatography/ion trap mass spectrometry

A reversed-phase liquid chromatographic method combined with fluorescence and multiple mass spectrometric detection in series is presented for the separation and structure elucidation of bisphenol A diglycidyl ether (BADGE) and novolac glycidyl ether (NOGE) derivatives. Atmospheric pressure chemical ionization in the positive ion mode and collision induced fragmentation in the ion trap allowed identification of BADGE- and NOGE-related compounds originating from reactions of the glycidyl ethers with bisphenols, solvents, and chain stoppers. Two extracts from food-can coatings were investigated in detail. It was possible to elucidate the structures of many substances and consequently to draw conclusions about the production of the lacquers.     

Simultaneous determination of NOGE-related and BADGE-related compounds in canned food by ultra-performance liquid chromatography–tandem mass spectrometry

An improved analytical method enabling rapid and accurate determination and identification of bisphenol F diglycidyl ether (novolac glycidyl ether 2-ring), novolac glycidyl ether 3-ring, novolac glycidyl ether 4-ring, novolac glycidyl ether 5-ring, novolac glycidyl ether 6-ring, bisphenol A diglycidyl ether, bisphenol A (2,3-dihydroxypropyl) glycidyl ether, bisphenol A (3-chloro-2-hydroxypropyl) glycidyl ether, bisphenol A bis(3-chloro-2-hydroxypropyl) ether, and bisphenol A (3-chloro-2-hydroxypropyl) (2,3-dihydroxypropyl) ether in canned food and their contact packaging materials has been developed by using, for the first time, ultra-performance liquid chromatography coupled with tandem mass spectrometry. After comparison of electrospray ionization and atmospheric pressure chemical ionization in positive and negative-ion modes, tandem mass spectrometry with positive electrospray ionization was chosen to carry out selective multiple reaction monitoring analysis of novolac glycidyl ethers, bisphenol A diglycidyl ether, and its derivatives. The analysis time is only 5.5 min per run. Limits of detection varied from 0.01 to 0.20 ng g(-1) for the different target compounds on the basis of a signal-to-noise ratio (S/N) = 3; limits of quantitation were from 0.03 to 0.66 ng g(-1). The relative standard deviation for repeatability was <8.01%. Analytical recovery ranged from 87.60 to 108.93%. This method was successfully applied to twenty samples of canned food and their contact packaging materials for determination of migration of NOGE, BADGE, and their derivatives from can coatings into food.     

液相色谱-串联质谱法测定小型家用电器塑料部件中双酚A

建立了小型家用电器塑料部件中双酚A的液相色谱-串联质谱(LC-MS/MS)检测方法。采用快速溶剂萃取仪对样品进行萃取,以Sep-Pak C18固相萃取柱净化,甲醇-水(含有0.05%氨水)混合液作为流动相,负离子模式下进行MS/MS检测。结果表明: 该方法在5～100 μg/L范围内线性关系良好,相关系数(r2)为0.9991。在10、25和75 μg/kg 3个添加水平下,双酚A的平均回收率为95.2%～109.7%,相对标准偏差均小于3.8%,检出限为10 μg/kg。该方法操作简便,灵敏度高,适用于家用电器塑料部件中双酚A的残留分析。     

Determination of alkylphenol and bisphenol A in beverages using liquid chromatography/electrospray ionization tandem mass spectrometry

A comprehensive analytical method based on liquid chromatography electrospray ionization tandem mass spectrometry (LC–ESI–MS/MS) with negative ionization mode has been developed for measuring of alkylphenols and bisphenol A in beverage samples. Concentration and clean up of samples were performed on 200 mg OASIS HLB solid extraction cartridges. The effects of mobile phases and additives on ionization were assessed. The recoveries for each compound ranged from 76.7 to 96.9% and reproducibilities were represented as having relative standard deviation (R.S.D.) below 10%. The limits of quantification (LOQ) of the method under multiple-reaction monitoring (MRM) acquisition mode were 0.04, 0.03 and 0.2 ng L⁻¹ for 2 L of mineral drinking water and 2.0, 1.8 and 8.0 ng L⁻¹ for 50 mL of soda beverages.     

Use of solid-phase microextraction for the analysis of bisphenol A and bisphenol A diglycidyl ether in food simulants

A new method has been developed to simultaneously analyse bisphenol A (BPA) and bisphenol A diglycidyl ether (BADGE) in aqueous based food simulants. The method consists on direct immersion solid-phase microextraction (SPME) of the analytes from the liquid matrix and subsequent chromatographic analysis by gas chromatography-mass spectrometry. Using the proposed method, a whole analysis (including chromatographic step) can be completed in less than 40 min, with minimum sample handling. The SPME method shows good analytical performance for simultaneous BPA and BADGE analysis, except for BADGE determination in the aqueous alcohol (simulant C) solution. Detection limits ranging from 0.1 to 2.0 ng/g for BPA and from 13 to 15 ng/g from BADGE were obtained, with a linear range from the low-ng/g to several-microg/g range for BPA and from 0.1 microg/g to 40 microg/g for BADGE. A possible optimisation method has been also developed and introduced.     

High-performance liquid chromatography-electrospray ionization mass spectrometry determination of mitiglinide in human plasma and its pharmacokinetics

A selective and sensitive method employing high-performance liquid chromatography-electrospray ionization mass spectrometry was developed and validated for the determination of mitiglinide in human plasma.With gliclazide as the internal standard, mitiglinide was extracted from plasma with n-hexane: = 80 : 20 (v/v). The organic layer was evaporated and the residue was redissolved in methanol: water (10 mM CH3COONH4, pH = 3.0) = 65 : 35 (v/v). An aliquot of 10 microl was chromatographically analyzed on a prepacked Shimadzu VP-ODS (5 microm, 150 x 2.0 mm i.d.) using the mobile phase comprising methanol: water (10 mM CH3COONH4) = 65 : 35 (v/v) by means of selected-ion monitoring mode mass spectrometry. Standard curves were linear (r2 = 0.9972) over the concentration range of 2.84-11 300 pmol/ml and had good accuracy and precision. The within- and between-batch precisions of the method were within 15% of standard deviation. The lower limit of detection was 1.42 pmol/ml. The validated HPLC/ESI-MS method has been successfully applied in the pharmacokinetics of mitiglinide in 12 healthy Chinese volunteers.     

Quantitation of free and total bisphenol A in human urine using liquid chromatography-tandem mass spectrometry

Bisphenol A (BPA) is employed in the synthesis of polycarbonate plastics and epoxy resins and is widely used in consumer products including as a coating for the inside of almost all food and beverage containers and thermal-imaging paper. Bisphenol A is considered to have important health implications because it possesses weak estrogenic activity and can leach from storage containers resulting in its consumption by both humans and animals. It is metabolized in the body and excreted into urine as a glucuronide derivative. In this report, we present an accurate, selective, sensitive, and reproducible high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) method for the quantitation of BPA in human urine, which is not prone to exogenous contamination. BPA-glucuronide is hydrolyzed enzymatically, extracted with toluene, derivatized with dansyl chloride, and the BPA-(dansyl)(2) derivative is analyzed using reversed-phase HPLC/MS/MS. Calibration was linear to 50 ng/mL with a limit of quantitation of 50 pg/mL and a limit of detection of 5 pg/mL.