紫外/TiO2/芬顿复合工艺增强在近中性pH值下对布洛芬的降解能力

药品及个人护理品(PPCPs)造成的潜在环境污染已引起广泛关注. 布洛芬(IBP, 2-(4-异丁基苯基)丙酸)作为苯丙酸类非甾体抗炎药物, 是一种在水环境中广泛检测到的PPCPs类物质. 水环境中的IBP主要来自制药企业排放和人体代谢物, 因IBP具有不易挥发、物理性质稳定、半衰期较长和不易被生物吸收等特点, 其在环境的残留浓度较高且污染风险大. 目前,传统的水处理工艺并不能有效治理水中的IBP, 比如: 混凝剂和絮凝剂对IBP的去除效率低, 吸附和膜处理运行成本过高且不能矿化IBP. 近年兴起的光催化技术利用·OH和O2·-等强氧化性活性物种降解水中有机污染物, 将其彻底矿化, 实现污染物的无害处理. 光催化技术适用于常温、常压和中性pH环境, 该环境特点与污水环境十分匹配, 适合应用. 但异质光催化通常发生在催化剂表面, 有效反应活性位少, 反应速率不够高. 相比而言, 同质芬顿反应能够均匀、快速地在整个溶液中发生反应, 但芬顿反应必须在酸性条件下才可以进行.本文整合了异相光催化和均相光-芬顿反应的优点, 设计了紫外/TiO2/芬顿(PCF)复合工艺, 评估了在中性pH下对典型的PPCPs布洛芬的降解效果. 对比实验结果表明, PCF复合工艺对IBP的降解速率比传统的UV, UV/H2O2, Fenton, 光-Fenton和光催化快得多. 动力学分析发现, IBP的降解遵循两阶段的一级反应动力学, 且速率常数k1> k2. 本研究进一步优化了运行参数, 确定IBP降解的最佳条件为: pH = 4.2, [Fe2+]0= 0.20 mmol/L, [Fe2+]0/[H2O2]0= 1/40, [TiO2]0= 1.0 g/L. pH值的增加造成IBP降解速率略微降低, 但在30 min反应时间内, 中性pH (6.0-8.0)与最佳pH条件下的降解效率完全相同, 证明PCF在中性pH下进行水处理切实可行. 数据分析发现, lnk1和lnk2均与1/pH0, [IBP]0, [H2O2]0, [H2O2]0/[Fe2+]0和ln[TiO2]0线性相关, 据此建立了IBP去除效率的数学预测模型, 通过验证发现, 动力学模型曲线与实验数据高度契合, 表明模型的有效性高.     

Highly sensitive method for the determination of 1-methyl-1,2,3,4-tetrahydro-beta-carboline using combined capillary gas chromatography and negative-ion chemical ionization mass spectrometry

A sensitive method was developed for the determination of deuterated and non-deuterated 1-methyl-1,2,3,4-tetrahydro-beta-carboline by combined capillary gas chromatography and negative-ion chemical ionization mass spectrometry. 1-Methyl-1,2,3,4-tetrahydro-beta-carboline was converted into a trifluoroacetyl derivative after pretreatment with fluorescamine and extraction with ethyl acetate. The derivative was separated by capillary gas chromatography and determined by selected-ion monitoring. In the determination, [3,3,4,4-2H4]-1-methyl-1,2,3,4-tetrahydro-beta-carboline was used as an internal standard. The method developed in this work was used for the determination of deuterated and non-deuterated 1-methyl-1,2,3,4-tetrahydro-beta-carboline in human urine samples collected before and after administration of [3,3-2H2]-L-tryptophan.     

High performance capillary electrophoresis method for determination of ibuprofen enantiomers in human serum and urine

A direct and stereospecific capillary zone electrophoresis (CZE) method for quantification ibuprofen enantiomers in biological matrices: human serum and urine, has been developed. Chiral separation of the enantiomers of ibuprofen and (+)-S-indobufen [(+)-S-INDB, internal standard, IS] was obtained in an uncoated silica capillary filled with a background electrolyte (BGE), consisted of heptakis 2,3,6-tri-O-methyl-β-cyclodextrin (TM-β-CD) in buffer of pH 5.0. The complete enantioselective analysis of ibuprofen and its 1-hydroxy metabolite confirmed appropriate specificity of the method. The electrophoretic parameters: electroosmotic (μ_EOF) and electrophoretic (μ_ep) mobility and resolution factor (R_s) were determined. Extraction procedures with organic solvent and solid phase extraction (SPE) with C₁₈ stationary phase for isolation of enantiomers from biological fluids were compared. SPE method for further studies was chosen. Stereoselective extraction of IBP enantiomers from serum at basic pH has been discovered. Validation of the method was carried out. Calibration curves of ibuprofen enantiomers were linear in the range of 0.1-25.0 μg/ml in serum and of 0.5-250.0 μg/ml in urine. Recovery of both enantiomers from serum and urine amounted 74-86 and 90-98%, respectively. Intra- and inter-day measurement precision and accuracy were below 15%. Limits of detection for IBP enantiomers amounted 0.05 and 0.25 μg/ml in samples of serum and urine, respectively. Limit of quantitation was also estimated. IBP enantiomers proved to be stable following three freeze and thaw cycles and during storage in autosampler at ambient temperature. The validated methods enable pharmacokinetic studies of enantiomers in both media. The elaborated HPCE method can be alternative to HPLC.     

Stable isotope dilution mass spectrometry for the simultaneous determination of cortisol, cortisone, prednisolone and prednisone in plasma.

A capillary gas chromatographic-mass spectrometric method for the simultaneous determination of cortisol, cortisone, prednisolone and prednisone in human plasma is described. [1,1,19,19,19-2H5]Cortisol, [1,1,19,19,19-2H5]cortisone, [1,19,19,19-2H4]prednisolone and [1,19,19,19-2H4]prednisone were used as internal standards. Formation of the bismethylenedioxy-3-heptafluoro-n-butyryl (BMD-HFB) derivatives made possible the separation of the four corticosteroids with good gas chromatographic behaviour. The new double derivatization has been demonstrated to be of value for sensitive and selective quantification by this technique. Detection was performed by monitoring the molecular ion (M+) of the BMD-HFB derivatives for cortisone and prednisolone, the [M - 18]+ ion for cortisol, and the [M - 30]+ ion for prednisone. The method requires no complex corrections for contributions and provides good accuracy and precision.     

Sensitive determination of deuterated and non-deuterated tryptophan, tryptamine and serotonin by combined capillary gas chromatography and negative ion chemical ionization mass spectrometry

Sensitive methods for the determination of deuterated and non-deuterated tryptophan, tryptamine and serotonin by combined capillary gas chromatography and negative ion chemical ionization mass spectrometry were developed. [3,3-2H2]-L-Tryptophan, which was used as a tracer, was synthesized for studies of their in vivo metabolism. Tryptophan was converted into its trifluoroacetylmethyl derivative after prepurification with an AG 50W-X2 cation-exchange column. Tryptamine and serotonin were extracted with 20% butanol in diethyl ether and derivatized with trifluoroacetic anhydride. These derivatives were separated and determined by selected ion monitoring. In these determinations, [2',3,3,4',5',6',7'-2H7]-D,L-tryptophan, [alpha,alpha,beta,beta-2H4]tryptamine and [alpha,alpha,beta,beta-2H4]serotonin were used as internal standards.     

Headspace sampling with in situ carbodiimide-mediated derivatization for the determination of ibuprofen in water samples

A method using headspace generation and in situ derivatization with water soluble EDC (1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide) and TFEA (2,2,2-trifluoroethylamine) has been optimized for the determination of ibuprofen (2-(p-isobutylphenyl)propionic acid), one of the most common non-steroid anti-inflammatory drug (NSAIDs) residues in surface and wastewater samples. Derivatization was carried out in the vial of the headspace sampler (HS) in only 15 min, after which instrumental measurements were made with gas chromatography-mass spectrometry (GC-MS). As the injection system, a programmed temperature vaporizer (PTV) in the solvent-vent injection mode is proposed in order to increase the sensitivity of the measurements. The effects of the variables affecting HS generation, the derivatization reaction, and the instrumental PTV conditions were studied. A limit of quantification as low as 32 ng/L was achieved, and repeatability values were below 10%. Accuracy of the method was evaluated using spiked ultrapure water at three concentration levels, obtaining apparent recoveries between 96% and 104%. The proposed method was applied to the quantification of ibuprofen in sea water and urban wastewater samples.     

Structural characteristics of activated carbons and ibuprofen adsorption affected by bovine serum albumin

Structural characteristics of a series of MAST carbons were studied using scanning electron microscopy images and the nitrogen adsorption isotherms analyzed with several models of pores and different adsorption equations. A developed model of pores as a mixture of gaps between spherical nanoparticles and slitlike pores was found appropriate for MAST carbons. Adsorption of ibuprofen [2-(4-isobutylphenyl)propionic acid] on activated carbons possessing different pore size distributions in protein-free and bovine serum albumin (BSA)-containing aqueous solutions reveals the importance of the contribution of mesopores to the total porosity of adsorbents. The influence of the mesoporosity increases when considering the removal of the drug from the protein-containing solution. Cellulose-coated microporous carbon Norit RBX adsorbs significantly smaller amounts of ibuprofen than uncoated micro/mesoporous MAST carbons whose adsorption capability increases with increasing mesoporosity and specific surface area, burnoff dependent variable. A similar effect of broad pores is observed on adsorption of fibrinogen on the same carbons. Analysis of the ibuprofen adsorption data using Langmuir and D'Arcy-Watt equations as the kernel of the Fredholm integral equation shows that the nonuniformity of ibuprofen adsorption complexes diminishes with the presence of BSA. This effect may be explained by a partial adsorption of ibuprofen onto protein molecules immobilized on carbon particles and blocking of a portion of narrow pores.     

Determination of the enantiomers of suprofen and [2H3]suprofen in plasma by capillary gas chromatography-mass spectrometry

A method for the stereoselective assay of the (+)- and (-)-enantiomers of suprofen and [2H3]suprofen in human plasma was developed using gas chromatography-mass spectrometry-selected-ion monitoring. (+/-)-[2H7]Suprofen was used as an internal standard. The method involved diethyl ether extraction and chiral derivatization with S-(-)-1-(naphthyl)ethylamine to form diastereomeric amide. The diastereoisomers were separated on a capillary gas chromatograph-mass spectrometer. Quantitation was achieved by selected-ion monitoring of the quasi-molecular ions of the diastereoisomers. The sensitivity, specificity, accuracy and reproducibility of the method were demonstrated to be satisfactory for application to pharmacokinetic studies of suprofen enantiomers.     

Quantitative determination of N-[trans-2-(dimethylamino)-cyclopentyl]-N-(3',4'-dichlorophenyl)propan amide, its 2H5-labeled analogue and their N-dealkylated metabolites in dog serum by capillary gas chromatography-mass spectrometry

This paper describes the development of a capillary gas chromatographic--mass spectrometric method for the determination of N-[trans-2-(dimethylamino)cyclopentyl]-N-(3',4'-dichlorophenyl)propan amide and its metabolites in serum. The method utilizes an automated sample preparation whereby drug, metabolites and internal standard are extracted from polar serum components by adsorption chromatography onto an XAD-type resin. The N-demethylated metabolites are derivatized by acetylation prior to chromatography. Detection is by mass spectrometry with chemical ionization. This method was utilized to determine levels of unlabeled and pentadeuterated drug and their respective metabolites in canine serum after oral co-administration. No significant kinetic isotope effects were observed for either absorption or metabolism.     

毛细管区带电泳法快速测定复方布洛芬片的有效成分

 研究了用毛细管区带电泳法快速测定复方布洛芬片中布洛芬和伪麻黄碱含量的方法。在０．０２５ｍｏｌ／Ｌ的磷酸盐缓冲液（ｐＨ８．１）中，上述两组分可在３ｍｉｎ内得以完全分离，用紫外检测器在２１０ｎｍ处检测，并以外标法定量。１１次测定含有９．５ｍｇ／Ｌ盐酸伪麻黄碱和６６．７ｍｇ／Ｌ布洛芬的试样溶液，相对标准偏差为２．９％（伪麻黄碱）和１．９％（布洛芬），回收率为１０３．１％（伪麻黄碱）和９７．６％（布洛芬）。应用毛细管区带电泳法测定复方布洛芬片剂的含量，所得结果与ＨＰＬＣ法一致。     

Simultaneous measurements of endogenous and deuterium-labelled tracer variants of androstenedione and testosterone by capillary gas chromatography-mass spectrometry

A capillary gas chromatographic-mass spectrometric method for the simultaneous determination of androstenedione and testosterone in human plasma using [19,19,19-2H3]androstenedione and [19,19,19-2H3]testosterone as internal standards is described. For calculation of plasma androstenedione and testosterone, peak heights were measured by selected-ion monitoring of the molecular ions of the heptafluorobutyryl derivatives of androstenedione and [2H3]androstenedione (m/z 482 and 485) and of testosterone and [2H3]testosterone (m/z 680 and 683). The isotope dilution method needed no complex corrections for contributions and provides a sensitive and reliable technique with good accuracy, precision and reproducibility.     

Simultaneous determination of cortisol and cortisone in human plasma by stable-isotope dilution mass spectrometry.

A method for the simultaneous determination of cortisol and cortisone in human plasma was developed using capillary gas chromatography-mass spectrometry-selected ion monitoring. [2H5]Cortisol and [2H5]cortisone were used as internal standards. Cortisol and cortisone in plasma were determined from the peak-height ratios of the [M-31] fragment ions of the methoxime-trimethylsilyl derivatives of cortisol and [2H5]cortisol (m/z 605 and 610) and of cortisone and [2H5]cortisone (m/z 531 and 536). Sensitivity, specificity, precision, accuracy and reproducibility of the method were demonstrated to be satisfactory for measuring the circulating concentrations of cortisol and cortisone.     

TLC chromatographic-densitometric assay of ibuprofen and its impurities

A simple and sensitive thin-layer chromatographic (TLC)-densitometric method for the quantitative estimation of S(+)-2-[4-isobutylphenyl]propionic acid (ibuprofen) and its impurities in pharmaceutical preparations has been developed. The chromatographic separation was carried out on silica gel 60 F(254) TLC plates using toluene-ethyl acetate-glacial acetic acid (17:13: 1, v/v/v) as the mobile phase. Detection was carried out densitometrically with a UV detector. The developed method has detection and quantitation limits ranging from 0.13 μg per spot to 0.72 μg per spot. For individual constituents the recovery ranged from 96.8% to 99.0%. In addition, the stability of ibuprofen solutions was investigated, including the effect of pH, temperature, and incubation time. The method is rapid, simple, and suitable for routine quality-control analysis of pharmaceuticals containing ibuprofen.     

Simultaneous determination of keto and non-keto bile acids in human serum by gas chromatography with selected ion monitoring

A reliable method for the simultaneous determination of keto and non-keto bile acids in human serum was developed. Carbonyl substituents of bile acid ethyl esters were converted into methyloxime and hydroxyl substituents into dimethylethylsilyl ethers and the products were analysed directly by capillary gas chromatography with selected ion monitoring using [2H4]chenodeoxycholic and [2H4]3 alpha-hydroxy-7-oxo-5 beta-cholanoic acids as internal standards. The bile acid peaks on the selected ion chromatogram were separated without interference from endogenous substances present in serum. Recoveries of individual keto bile acids added to serum range from 74.4 to 94.7% with a mean of 87.1%. Eight kinds of keto bile acids not previously found in sera of normal subjects, namely 3-oxo-, 3-oxo-7 alpha-hydroxy-, 3-oxo-12 alpha-hydroxy-, 3 alpha-hydroxy-7-oxo, 3 alpha-hydroxy-12-oxo-, 3-oxo-7 alpha,12 alpha-dihydroxy-, 3 alpha,7 alpha-dihydroxy-12-oxo- and 3 alpha,12 alpha-dihydroxy-7-oxo-5 beta-cholanoic acids were identified and quantified. The total concentration of keto bile acids was found to be 0.16 +/- 0.08 nmol/ml and constituted 2.9 +/- 1.5% of that of the usual non-keto bile acids in peripheral venous serum.     

Supercritical fluid extraction with in situ chiral derivatization for the enantiospecific determination of ibuprofen in urine samples

In situ chiral derivatization was used to obtain diastereomeric amides of ibuprofen for their subsequent extraction with supercritical carbon dioxide. For this purpose, ibuprofen [racemic 2-(4-isobutylphenyl)propionic acids] was previously extracted on a C-18 SPE device and quantitatively transferred into the supercritical fluid extraction (SFE) vessel for derivatization and extraction with (R)-1-(naphthen-1-yl)ethylamine as chiral derivatizing base, and a mixture of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide and 1-hydroxybenzotriazole as reagents, in order to obtain and extract the corresponding diastereoisomeric amides, which were subsequently determined by liquid chromatography. The influence of different extraction and derivatization variables (pressure, temperature, extraction time in the static and dynamic extraction modes, and amount of chiral base) on the extraction efficiency was studied. Spiked and native urine samples containing ibuprofen were used to demonstrate the application of this method. The absolute recovery, selectivity, precision and accuracy of the combined solid-phase extraction (SPE)/SFE approach were compared to those provided by conventional liquid–liquid extraction. The results indicated that SFE seems to be an effective choice for in situ derivatization since analysis times and solvent consumption were dramatically reduced.     

Hydrolysis of ibuprofen nitrile and ibuprofen amide and deracemisation of ibuprofen using Nocardia corallina B-276

A novel application of whole cells of Nocardia corallina B-276 for the deracemisation of ibuprofen is reported. This microorganism successfully hydrolysed ibuprofen nitrile to ibuprofen amide, and ibuprofen amide to ibuprofen, using a suspension of cells in a potassium phosphate buffer solution (0.1 M, pH = 7.0). These results can be explained by the presence of NHase and amidase enzymes, but the reactions are not enantioselective and low ee values were obtained. However, (R)-ibuprofen was isolated with > 99% ee by a deracemisation process catalysed by N. corallina B-276. This is the first report of this kind of catalysis with this microorganism.     

Competitive binding of small molecules with biopolymers: a fluorescence spectroscopy and chemometrics study of the interaction of aspirin and ibuprofen with BSA

The interaction of aspirin and ibuprofen with bovine serum albumin (BSA) was studied by spectrofluorimetry under simulated physiological conditions. Both aspirin and ibuprofen quenched the intrinsic fluorescence of BSA and the binding ratios obtained were 2 : 1 for aspirin-BSA and 3 : 1 for ibuprofen-BSA interactions, respectively. The thermodynamic parameters (ΔH, ΔS and ΔG) obtained from the fluorescence spectroscopy data showed that the binding of aspirin to BSA involved van der Waals interactions and hydrogen bonds. Competitive experiments using warfarin and diazepam as site markers indicated that aspirin was mainly located in the hydrophobic pocket of site II of the protein as well as to a small extent in site I. Furthermore, the competitive interaction of the aspirin and ibuprofen with BSA, which was studied with the use of the three-way excitation-emission fluorescence spectra and a parallel factor analysis (PARAFAC) chemometrics method, showed that the competitive effect of ibuprofen was stronger than that of aspirin, i.e. the former molecule replaced the aspirin from the aspirin-BSA complex.     

Determination of ibuprofen and tetrazepam in human urine by micellar electrokinetic capillary chromatography

A new micellar electrokinetic capillary chromatography method (MEKC) is proposed for the determination of ibuprofen and tetrazepam in human urine samples over a concentration range of therapeutic interest. A fused silica capillary (60 cm × 75 μm) is used. Ibuprofen and tetrazepam are detected via UV detection at 220 and 228 nm, respectively. Separation is performed at 25 °C and at a separation voltage of 30 kV, with 15 mM borate buffer (pH 10.2) containing 40 mM sodium dodecylsulfate as the electrolyte solution. Under these conditions the analytes were separated in <11 min. Sulfamethazine is used as an internal standard. Prior to determination, the samples are purified and enriched by means of an extraction–preconcentration step with a preconditioned C₁₈ cartridge and by eluting the compounds with methanol. Good linearity, accuracy, precision, robustness and solution stability were achieved for the technique. Detection limits of 200 μg L⁻¹ for ibuprofen and 300 μg L⁻¹ for tetrazepam were obtained. These analytes were then determined in real urine using the technique.     

Simultaneous determination of stable isotopically labelled L-histidine and urocanic acid in human plasma by stable isotope dilution mass spectrometry.

A capillary gas chromatographic-mass spectrometric method for the simultaneous determination of stable isotopically labelled L-histidine (L-[3,3-2H2,1',3'-15N2]histidine, L-His-[M + 4]) and urocanic acid ([3-2H,1',3'-15N2]urocanic acid, UA-[M + 3]) in human plasma was developed using DL-[2,3,3,5'-2H4,2'-13C,1',3'-15N2]histidine (DL-His-[M + 7]) and [2,3,5'-2H3,2'-13C,1',3'-15N2]urocanic acid (UA-[M + 6]) as internal standards. L-Histidine and urocanic acid were derivatized to alpha N-(trifluoroacetyl)-imN-(ethoxycarbonyl)-L-histidine n-butyl ester and imN-(ethoxycarbonyl)urocanic acid n-butyl ester. Quantification was carried out by selected ion monitoring of the molecular ions of the respective derivatives of L-His-[M + 4], DL-His-[M + 7], UA-[M + 3] and UA-[M + 6]. The sensitivity, specificity, precision and accuracy of the method were demonstrated to be satisfactory for measuring plasma concentrations of L-His-[M + 4] and UA-[M + 3] following administration of trace amounts of L-His-[M + 4] to humans.     

Determination of Metformin in Human Plasma by Liquid Chromatography-tandem Mass Spectrometric Assay

Introduction Metformin (1,1-dimethylbiguanide) (Fig. 1) is an oral anti-hyperglycemic agent used in the treatment of non-insulin-dependent diabetes mellitus (type Ⅱ). Owing to its weight-decreasing and serum lipid-normalizing effects, it is especially recommended for obese patients[1,2] Various analytical methods have been described for the measurement of metformin in biological fluids, including gas chromatography(GC)[3-5], capillary electrophoresis (CE)[6] and HPLC[7～16]with UV detection[7-12,17] HPLC-Mass spectrometry (LC/APCIMS/MS ) offers an attractive alternative to HPLC[18].