固相萃取结合超高效液相色谱-串联质谱法及气相色谱-负化学源质谱法测定人血清中的四溴双酚A、六溴环十二烷和多溴联苯醚

建立了固相萃取同时提取、净化血清中四溴双酚A(TBBPA)、α, β, γ-六溴环十二烷(HBCD)和8种多溴联苯醚(PBDEs)同系物的样本前处理方法,并结合色谱-质谱分离分析技术检测人血清样本中该类化合物的含量。试样在加入各自的同位素内标物后以甲基叔丁基醚/正己烷(1:1, v/v)混合溶剂进行萃取,再经浓硫酸去除脂肪后,以LC-Si固相萃取柱分离HBCD/TBBPA和PBDEs。采用分步检测的方式,在50 mm长BEH C18反相色谱柱上以超高效液相色谱-串联质谱(UPLC-MS/MS)的多反应监测模式(MRM)检测HBCD和TBBPA,在15 m长的毛细管柱上以气相色谱-负化学源质谱(GC-NCI/MS)的选择离子监测模式(SIM)检测PBDEs。以胎牛血清为空白基质,当HBCD、TBBPA和BDE-209的加标水平为0.5 ng/g和5 ng/g、三溴至七溴联苯醚的加标水平为0.05 ng/g和0.5 ng/g时,它们的平均加标回收率为80.3%～108.8%,相对标准偏差为1.02%～11.42%(n=5);以信噪比(S/N)为3计算,方法的检出限(LOD)为1.81～42.16 pg/g。采用该方法对实际样品进行测定,结果表明,本方法快速、准确、灵敏度高,能够满足血清中HBCD、TBBPA和PBDEs残留的同时提取及测定的要求。     

Liquid chromatography-mass spectrometry identification of imidacloprid photolysis products

Photolysis of imidacloprid by near ultraviolet (UV) radiation was investigated using reversed phase liquid chromatography (RPLC) and liquid chromatography-electrospray ionization/mass spectrometry (LC-ESI/MS) operated in the positive ion mode. The decomposition of imidacloprid by near UV light is first order with a half life of 10.18 h. Photo-degradation products of imidacloprid identified in this study included imidacloprid urea, imidacloprid olefin, and imidacloprid desnitro. A degradation pathway is proposed for imidacloprid from an examination of the product decay curves obtained in this monitoring study which was performed in a batch test mode.     

Gas chromatography-mass spectrometry/mass spectrometry analysis to determine natural and post-administration levels of oestrogens in bovine serum and urine

A novel analytical approach has been developed and shown to be capable of detecting the isomers of oestradiol in the low ppt (pg mL(-1)) range in bovine serum and urine. Following extractive derivatisation the analytes were detected as their 3-pentafluorobenzoyl 17-trimethylsilyl ether derivatives by gas chromatography-mass spectrometry/mass spectrometry (GC-MS/MS), using electron capture negative ion chemical ionisation. The isomers of oestradiol were quantified in both blank and post-administration urine and serum samples, with a view to setting action/threshold levels for these compounds, to allow discrimination between normal samples and samples from animals treated with growth promoting ear implants. A non-parametric statistical assessment of the data resulted in proposed action levels (with a false positive probability of 1 in 1000) of 1.6 and 2.7 ng mL(-1) for 17alpha-oestradiol, in male and female urine, respectively, and 40 and 44 pg mL(-1) for 17beta-oestradiol, in male and female urine, respectively. An action level of 20 pg mL(-1) was proposed for 17alpha- and 17beta-oestradiol in male serum. In female serum the proposed action levels were 40 and 20 pg mL(-1) for 17alpha- and 17beta-oestradiol, respectively.     

Determination of hexabromocyclododecane diastereoisomers in air and soil by liquid chromatography-electrospray tandem mass spectrometry

Hexabromocyclododecanes (HBCDs), used as additive brominated flame retardants, are of high concern due to their widespread use and increasing levels in various environmental systems. High-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC-MS/MS) was developed for the determination of HBCD diastereoisomers. A detailed study was carried out to optimize the composition of the mobile phase involving methanol/acetonitrile/water, and the values of MS/MS parameters. It was found that the mobile phase could simultaneously affect the chromatographic separation and sensitivity. The instrumental limits of detection (LODs) on column in this study were 0.5, 0.3 and 0.3 pg for alpha-HBCD, beta-HBCD and gamma-HBCD, respectively. The effects of extracted matrix components on HBCD determination were investigated by spiking air and soil sample extracts with three 13C-labelled individual stereoisomers. The results indicated that the responses of the HBCD analysis in air and soils were not significantly affected by matrix effects. The method reported here was further applied to the air and soil samples. Three HBCD diastereoisomers were detected in all the air and soil samples, with levels ranging from 1.2 to 1.8 pg/m3 and 1.7 to 5.6 ng/g dry weight, respectively.     

Determination of ink photoinitiators in packaged beverages by gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry

A new analytical method, using gas chromatography-mass spectrometry (GC/MS) and liquid chromatography-mass spectrometry (LC/MS) techniques, was developed for the determination in packaged food beverages of five ink photoinitiator residues: 2-isopropylthioxanthone (ITX), benzophenone, 2-ethylhexyl-4-dimethylaminobenzoate (EHDAB), 1-hydroxycyclohexyl-1-phenyl ketone (IRGACURE 184) and ethyl-4-dimethylaminobenzoate (EDAB). Samples were extracted from selected beverages (milk, fruit juices and wine) and relative packagings, using n-hexane and dichloromethane, respectively, purified on solid-phase extraction (SPE) silica gel cartridges, and then analyzed in GC/MS and LC/MS. The recovery percentages, obtained spiking the beverage samples at concentrations of 4 and 10 microgl(-1) with a standard mixture of photoinitiators, were in the range 42-108% (milk), 50-84% (wine), and 48-109% (fruit juices). The repeatability of the method was assessed in all cases by the % of correlation value, that was lower than 19%. The lowest limits of detection (LODs) and limits of quantification (LOQs), obtained using GC/MS, were in the range 0.2-1 and 1-5 microgl(-1), respectively. The method was applied to the analysis of forty packaged food beverages (milk, fruit juices and wine samples). The most significant contamination was that of benzophenone, found in all samples in a concentration range of 5-217mugl(-1). Its presence was confirmed by an LC/Atmospheric-Pressure PhotoIonization (APPI)/MS/MS analysis. The photoinitiator (EHDAB) was found in eleven out of forty beverages in a concentration range of 0.13-0.8 microgl(-1). Less important was the ITX contamination, found in three out of forty samples in a range 0.2-0.24 microgl(-1). The work proposes a new method to analyze ink photoinitiator residues in polycoupled carton packaging and in contained food beverages.     

超高效液相色谱-电喷雾质谱法结合同位素稀释技术检测动物源性食品中的六溴环十二烷异构体

建立了使用超高效液相色谱-电喷雾四极杆质谱(UPLC-ESI-MS)结合同位素稀释技术准确测定动物源性食品中六溴环十二烷(HBCD)的3种非对映异构体的方法。试样在加入同位素内标13C-HBCD后进行索氏提取,提取液去除脂肪后经硅胶固相萃取柱浓缩、净化后,通过Waters ACQUITY UPLCTM BEH C18色谱柱分离,以甲醇-乙腈混合液和水为流动相进行梯度洗脱。在UPLC-MS分析过程中以保留时间和母离子信息进行定性,选择离子记录(SIR)方式定量。该法对于所测试的鲜奶、鱼肉等样品,检出限为0.1～0.4 ng/g,定量限为0.4～1.2 ng/g。对于加标鱼肉样品,添加水平为0.6,2.0和6.0 ng/g时,3种被测物的加标回收率为92.9%～99.3%,相对标准偏差为3.1%～8.0%。     

Discrimination of cyclic peptide diastereomers by electrospray ionization tandem mass spectrometry

In this research, the characteristic ions' abundance ratio between two isomers A and B in MS/MS mass spectra was defined as a parameter for discriminating diastereomers. Through this ratio, the discrimination of four pairs of cyclic peptide (CP) diastereomers was successfully achieved. Furthermore, in the analysis of diastereomers' mixtures, both calibration curve and calculational methods were substantiated to have high precision and accuracy. The average absolute errors of the two methods were 2.0 and 2.5% in the 48 measurements of 16 samples, respectively. This research provided a promising approach for the analysis of the CP diastereomers in the fields of asymmetrical synthesis, chiral natural products and structural biology by ESI‐MS/MS. Copyright © 2009 John Wiley & Sons, Ltd.     

液相色谱-电喷雾电离质谱法检测尿液中的3种合成类固醇药物

研究建立了合成类固醇药物群勃龙、四氢孕三烯炔酮和孕三烯酮的液相色谱-电喷雾质谱的检测方法。尿样经过β-葡萄糖醛酸酶酶解和叔丁基甲醚提取后,采用Zorbax SB-C18分析柱(150 mm×2.1 mm,5 μm),在流动相为pH 3.5的甲酸铵缓冲液-乙腈的条件下进行梯度洗脱,在正离子模式下检测。考察了不同的质谱条件对这类化合物检测结果的影响。建立了人尿液中合成类固醇药物的液相色谱-电喷雾电离质谱的初筛和确证方法。     

Trace determination of hexabromocyclododecane diastereomers in water samples with temperature controlled ionic liquid dispersive liquid phase microextraction

A novel temperature controlled ionic liquid dispersive liquid phase microextraction(TCIL-DLPME) coupled with rapid resolution liquid chromatography-electrospray tandem mass spectrometry(RRLC-ESI-MS-MS) has been developed for the enrichment and determination of three hexabromocyclododecane diastereomers(HBCDs) in water samples.Green solvent ionic liquid(IL) was used as extraction solvent instead of toxic organic solvents.This technique also avoided the usage of dispersive solvent.Some important parameters that might affect the extraction efficiency were optimized.Under the optimum conditions,good linear relationship,sensitivity and reproducibility were obtained.All the limits of detection for the three diastereomers were 0.1 ng/ mL.The linear range was obtained in the range of 1-100 ng/mL for the total amount of three HBCD diastereomers.It was satisfactory to analyze real environmental water samples with the recoveries ranging from 77.2%to 99.3%.The main advantage of the method is toxic organic solvent-free.     

Simultaneous determination of bisphenol A, triclosan, and tetrabromobisphenol A in human serum using solid-phase extraction and gas chromatography-electron capture negative-ionization mass spectrometry

This study aimed at optimizing and validating a sensitive method for simultaneous determination of bisphenol A (BPA), triclosan (TCS), and tetrabromobisphenol A (TBBPA) in human serum using solid-phase extraction (SPE) and gas chromatography coupled to electron-capture negative-ionization mass spectrometry (GC-ECNI/MS). Sample preparation involved denaturation of serum proteins with formic acid followed by SPE on an Oasis HLB cartridge. Fractionation was performed on Florisil from which the phenolic compounds were eluted with methanol-dichloromethane (DCM) (5:1, v/v). The phenolic fraction was further derivatized with pentafluoropropionic acid anhydride (30 min at 70 degrees C). Further liquid-liquid partitioning using hexane-DCM (4:1, v/v) and K(2)CO(3) 3% aqueous solution was used to eliminate excess reagent and acidic by-products formed during derivatization. The cleaned extract was injected into a GC-ECNI/MS system operated in selected ion monitoring mode. For thorough method validation, each step of the procedure was rigorously optimized. The method limits of quantitation for BPA, TCS, and TBBPA were 0.28 ng mL(-1), 0.09 ng mL(-1) and 0.05 ng mL(-1), respectively. Furthermore, the method was applied to 21 Belgian human serum samples. The median concentrations obtained for BPA (0.71 ng mL(-1)) and TCS (0.52 ng mL(-1)) in Belgian human serum samples were similar to previously reported data for human fluids. Slightly higher levels of TBBPA (0.08 ng mL(-1)) were found in Belgium samples compared to Norwegian serum.     

Quantification of zolpidem in human plasma by liquid chromatography-electrospray ionization tandem mass spectrometry

A simple and robust method for quantification of zolpidem in human plasma has been established using liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI MS/MS). Es-citalopram was used as an internal standard. Zolpidem and internal standard in plasma sample were extracted using solid-phase extraction cartridges (Oasis HLB, 1 cm3/30 mg). The samples were injected into a C8 reversed-phase column and the mobile phase used was acetonitrile-ammonium acetate (pH 4.6; 10 mm) (80:20, v/v) at a flow rate of 0.7 mL/min. Using MS/MS in the selected reaction-monitoring (SRM) mode, zolpidem and Es-citalopram were detected without any interference from human plasma matrix. Zolpidem produced a protonated precursor ion ([M+H]+) at m/z 308.1 and a corresponding product ion at m/z 235.1. The internal standard produced a protonated precursor ion ([M+H]+) at m/z 325.1 and a corresponding product ion at m/z 262.1. Detection of zolpidem in human plasma by the LC-ESI MS/MS method was accurate and precise with a quantification limit of 2.5 ng/mL. The proposed method was validated in the linear range 2.5-300 ng/mL. Reproducibility, recovery and stability of the method were evaluated. The method has been successfully applied to bioequivalence studies of zolpidem.     

六溴环十二烷的样品前处理和检测方法研究进展北大核心CSCD

作为一种常见的溴代阻燃剂,六溴环十二烷(HBCDs)因具备持久性、长距离迁移性、生物蓄积性和高毒性,于2013年被列入《斯德哥尔摩公约》。因此,环境样品中HBCDs污染水平的准确分析和严格控制对完善环境监管长效机制至关重要。然而,实际样品中HBCDs的定性定量分析正面临着基质复杂、目标物含量低等问题。尤其,HBCDs在高温环境及特定有机溶剂中易降解,会产生异构体,提高了分析难度。该综述简述了HBCDs的理化性质、毒性危害和标准限制,重点围绕不同基质中HBCDs的样品前处理和仪器检测两方面进行了总结。论文内容引用2000~2022年的70余篇源于科学引文索引(SCI)与中文核心期刊中的相关论文。总结归纳了固体和液体样品中HBCDs分析的前处理技术,包括索式提取、超声辅助萃取、加速溶剂萃取、超临界流体萃取、液液萃取、分散液液微萃取、固相萃取、分散固相萃取和固相微萃取等,介绍了气相色谱、液相色谱和色谱-质谱联用技术等仪器检测方法在HBCDs分析中的应用。通过综述近期相关研究,侧面表明HBCDs的分析方法研究发展迅速,但也面临一些挑战,如样品前处理步骤繁琐、耗时长、样品量和有机溶剂用量大等问题。最后,对新型样品前处理技术在HBCDs分析中的应用进行了展望。     

Clean-up method for determination of established and emerging brominated flame retardants in dust

A clean-up method was developed to enable the determination of tri-decabrominated diphenyl ethers, isomer-specific hexabromocyclododecanes (HBCDs), 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE), decabromodiphenyl ethane (DBDPE), (2-ethylhexyl)tetrabromobenzoate (TBB), and bis(2-ethylhexyl)tetrabromophthalate (TBPH) in the same dust sample extract using reasonable amounts of solvents and without dividing the sample. After extraction, the sample was separated on a silica column into three fractions that were subsequently cleaned up individually. The polybrominated diphenyl ethers (PBDEs) and DBDPE were eluted in Fraction I, TBB, TBPH, and BTBPE in Fraction II, and HBCDs in Fraction III. Fractions I and II were analyzed using gas chromatography/mass spectrometry and Fraction III using liquid chromatography/mass spectrometry. The method gave good recoveries (60-120%), precise results using (13)?C-labelled internal standards and was accurate when comparing results to certified values (PBDEs in NIST SRM 2585). The method was applied to dust samples from the Stockholm (Sweden) area. All the emerging brominated flame retardants (BFRs) studied, except BTBPE, were present in all the samples in quantifiable concentrations, often higher than the PBDEs. BTBPE was quantified in only one sample. It is evident that emerging BFRs are present in Swedish homes, and these compounds should be included in the BFR analyses of indoor environments.     

Analysis of high-mannose-type oligosaccharides by microliquid chromatography-mass spectrometry and capillary electrophoresis

We report on microbore liquid chromatography (microLC) and capillary electrophoresis (CE) separation of glycopeptides and high-mannose-type oligosaccharides, digested from recombinant phospholipase C, expressed in Pichia pastoris. The glycopeptides were subject to microLC/electrospray ionization/mass spectrometry (ESI-MS) and microLC/ESI-tandem MS (MS/MS) analysis that revealed high-mannose structure size variation between Man(7)GlcNAc(2) and Man(14)GlcNAc(2). Then, high-performance CE was applied to identify possible positional isomers of the high-mannose structures. For the CE experiments, the oligosaccharides were released from the glycoproteins by peptide-N-glycosidase F and labeled with 1-aminopyrene-3,6,8-trisulfonic acid (APTS). Excellent separation of the possible positional isomers was attained, suggesting one for Man(9)GlcNAc(2), two for Man(10)GlcNAc(2), three for Man(11)GlcNAc(2), Man(12)GlcNAc(2), and Man(13)GlcNAc(2), and two for Man(14)GlcNAc(2). The CE results provided complementary information to the microLC/ESI-MS and MS/MS data with respect to the possible number of positional isomers.     

Quantitative analysis of eight testosterone metabolites using column switching and liquid chromatography/tandem mass spectrometry

The rate at which testosterone is metabolized to different singly hydroxylated metabolites has been widely used as an in vitro marker for activity of different CYP450 enzymes. The interest in extra-hepatic metabolism, e.g. due to metabolism in the gut wall, has increased during the last decade. Measurement of extra-hepatic enzyme activity using testosterone as a substrate requires a highly sensitive analytical method. A new liquid chromatography/electrospray tandem mass spectrometry (LC/MS/MS) method, using column switching for online cleaning and desalting of samples, was developed and validated for analysis of 2alpha-, 2beta-, 6alpha-, 6beta-, 7alpha-, 16alpha-, and 16beta-hydroxytestosterone and androstenedione. The samples were injected on a SB-CN column and detection was performed using MS/MS. The limits of quantification ranged from 0.3 to 3.33 nM for the different metabolites. The validated method was used to quantify the enzyme activity in rat intestine mucosa. The formation rates of 16alpha-, 16beta-hydroxytestosterone and androstenedione were quantified, and 2beta-and 6beta-hydroxytestosterone were formed above the limits of detection.     

高效液相色谱-电喷雾质谱法测定环境大气中的六溴环十二烷

优化了环境大气样品前处理步骤中复合硅胶柱的净化条件,建立了高效液相色谱-电喷雾-质谱(HPLC-ESIMS)测定环境大气中六溴环十二烷(hexabromocyclododecanes,HBCDs)的分析方法。样品经正己烷提取后,采用复合硅胶柱净化,以50 mL正己烷和100 mL正己烷-二氯甲烷(9∶1,v/v)为淋洗液,以180 mL正己烷-二氯甲烷(4∶1,v/v)为洗脱液。采用UF-ODS柱(150 mm×2.1 mm,3.0μm),以乙腈-甲醇-水为流动相进行梯度洗脱,在电喷雾负离子源、选择离子监测(SIM)模式下检测。在优化的条件下,α-HBCD、β-HBCD和γ-HBCD能很好地分离,在1~100μg/L范围内,α-HBCD、β-HBCD和γ-HBCD与进样内标D_(18)-γ-HBCD峰面积的比值与对应的质量浓度均具有良好的线性关系,相关系数(R)≥0.998 8。α-HBCD、β-HBCD和γ-HBCD的仪器检出限(S/N=3)分别为0.4、0.5和0.4μg/L;定量限(S/N=10)分别为1.4、1.6和1.3μg/L;方法检出限(MDL)分别为0.13、0.17和0.13pg/m~3(n=5);实际样品的加标回收率为74.8%~95.8%。该法灵敏度高,选择性好,可以满足大气样品中HBCDs的监测和分析需求。     

Fragmentations of isomeric sulfated monosaccharides using electrospray ion trap mass spectrometry

Electrospray ionization combined with ion trap mass spectrometry (ESI-ITMS) is a powerful tool for structural analysis of complex carbohydrates. Although its application to sulfated glycans has been limited so far, it should provide critical information, such as sulfate positions, on their structures. In this work, MS(n) spectra of nine monosulfated monosaccharides, consisting of five hexoses and four N-acetylhexosamines, were measured in negative ion mode to find basic fragmentation rules for sulfated sugars. Two pairs of positional isomers with respect to sulfation, i.e., Gal4S and Gal6S, and GalNAc4S and GalNAc6S, showed characteristic fragmentation patterns in MS(3), and could be discriminated from one another by the appearance of particular diagnostic fragment ions that characterize individual isomers. It was also demonstrated that, even if a mixture of these positional isomers was analyzed, the proportion of each species could be estimated through analysis of the abundance ratios of the diagnostic ions. However, 3-O-sulfated saccharides (Glc3S and GlcNAc3S) gave a single abundant diagnostic ion in MS(2) corresponding to the hydrogensulfate ion, [OSO(3)H](-), and this characteristic clearly differentiated them from their positional isomers. In contrast, 6-O-sulfated diastereomers consisting of two groups, Glc6S, Man6S, Gal6S, and GlcNAc6S, GalNAc6S, could not be discriminated by the types of fragment ions; however, the abundance ratios of particular fragment ions differed significantly between Glc(NAc)6S and Gal(NAc)6S. Since ESI-ITMS yielded large quantities of useful information on structures of monosulfated hexoses and N-acetylhexosamines in an extremely simple and reproducible manner, establishment of a comprehensive strategy based on ESI-ITMS(n) appears to be a promising technique for structural elucidation of sulfated complex carbohydrates.     

Determination of triazine pesticides and related compounds in environmental water by liquid chromatography-mass spectrometry.

A method for the determination of 5 triazine herbicides and 12 degradation products in environmental water samples using liquid chromatography-electrospray ionization mass spectrometry (LC/ESI/MS) has been developed. The pesticides in water were extracted with two types of solid phase: a styrene-divinylbenzene copolymer and a graphitized carbon black. Desorption solvents for the extracted compounds were acetone for the styrene-divinylbenzene copolymer and methanol for the graphitized carbon black. Overall recoveries from ground water and river water ranged from 73% to 111%. The limits of detection (LODs) were 0.2 to 28 ng l(-1). This method was applied to several ground water samples.     

Determination of naphthalenesulfonic acid isomers by large-volume on-line derivatization and gas chromatography-mass spectrometry

This work presents a modified method to analyze polar and water-soluble naphthalene monosulfonic acid (NS) isomers in industrial effluents and river water samples. The method involves extraction of samples by a styrene-divinylbenzene copolymer solid-phase extraction cartridge, and on-line derivatization in the GC injection port using a large-volume (10 microl) sample injection with tetrabutylammonium salts. The analytes were then identified and quantitatively determined by GC-MS. The large-volume injection-port derivatization technique provides sensitivity, fast and reproducible results for NS isomers, to quantitation at 0.05 microg/l in 200 ml of water sample. Enhanced extracted mass chromatograms of molecular ion and [M-56]+ ion of butylated NS isomers by electron impact ionization MS allows us to determine residues at trace levels in environmental samples. Recoveries of the NS isomers in spiked water samples ranged from 70 to 82% with RSDs around 10%. Naphthalene-2-sulfonic acid was found as a major pollutant and propagated in surface water and industrial effluents.     

气相色谱-质谱联用法对6-溴-去氢甲基睾丸素合成过程中杂质的分析

采用气相色谱-质谱联用方法分析6-溴-去氢甲基睾丸素中的杂质。在30.0m×0.25mm,0.5μm的ZB-5MS毛细管柱上,柱温100℃保持3 min,后以20℃/min的速率程序升温至250℃,气化室温度270℃,载气氦气流量0.8 mL/min的条件下,6-溴-去氢甲基睾丸素及其中杂质获得很好分离。通过对各组分质谱图分析确定了6-溴-去氢甲基睾丸素中的七种杂质分别为去氢甲基睾丸素,6-烯-去氢甲基睾丸素,6-溴-17-甲基雄甾-1,4,16-三烯-3-酮的4种构象异构体以及6-溴-8-烯-去氢甲基睾丸素。