Wide‐scope analysis of pesticide and veterinary drug residues in meat matrices by high resolution MS: detection and identification using Exactive‐Orbitrap

A multiresidue and multiclass method for the simultaneous determination of more than 350 compounds including pesticides, biopesticides and veterinary drugs in different meat matrices (beef, pork and chicken) by ultra‐high performance liquid chromatography coupled to Orbitrap MS has been developed. In the present study, the determination of fragments was accomplished as an essential tool for a reliable identification of compounds using high resolution MS. To obtain these fragments, different strategies have been carried out in order to ensure an appropriate fragment assignment and identification. The analytical method is suitable for qualitative analysis, and it was also evaluated for quantitative analysis. Generic extraction conditions were optimized, obtaining adequate recovery and precision values for most of the studied analytes (>290). The limits of detection ranged from 2 to 16 µg kg^?1. Limits of quantification were 10 µg kg^?1 with the exception of few compounds with a higher value (50 or 100 µg kg^?1). Limits of identification were also established, and they ranged from 2 to 150 µg kg^?1. This method was applied to the analysis of 18 meat samples and some veterinary drugs as enrofloxacin and sulfadiazine were detected and further identified/quantified (with triple quadrupole) in two different samples at 33 µg kg^?1 and trace levels, respectively. No pesticides were detected in the analyzed samples. Copyright © 2014 John Wiley & Sons, Ltd.     

Determination of polychlorinated biphenyls by liquid chromatography–atmospheric pressure photoionization–mass spectrometry

This study presents the atmospheric pressure photoionization (APPI) of high‐chlorinated (five or more chlorine atoms) polychlorinated biphenyls (PCBs) using toluene as dopant, after liquid chromatographic separation. Mass spectra of PCB 101, 118, 138, 153, 180, 199, 206 and 209 were recorded by using liquid chromatography‐APPI‐tandem mass spectrometry (LC‐APPI‐MS/MS) in negative ion full scan mode. Intense peaks appeared at m/z that correspond to [M ? Cl + O]^? ions, where M is the analyte molecule. Furthermore, a detailed strategy, which includes designs of experiments, for the development and optimization of LC‐APPI‐MS/MS methods is described. Following this strategy, a sensitive and accurate method with low instrumental limits of detection, ranging from 0.29 pg for PCB 209 to 8.3 pg for PCB 101 on column, was developed. For the separation of the analytes, a Waters XSELECT HSS T3 (100 mm × 2.1 mm, 2.5 µm) column was used with methanol/water as elution system. This method was applied for the determination of the above PCBs in water samples (surface water, tap water and treated wastewater). For the extraction of PCBs from water samples, a simple liquid–liquid extraction with dichloromethane was used. Method limits of quantification, ranged from 4.8 ng l^?1, for PCB 199, to 9.4 ng l^?1, for PCB 180, and the recoveries ranged from 73%, for PCB 101, to 96%, for PCB 199. The estimated analytical figures were appropriate for trace analysis of high‐chlorinated PCBs in real samples. Copyright © 2014 John Wiley & Sons, Ltd.     

A novel LC‐MS/MS method for determination of tissue distribution and excretion of timosaponin B‐II in rat biological matrices

Timosaponin B‐II (TB‐II) is a natural bioactive steroid glycoside extracted from the Chinese medicinal herb Anemarrhena asphodeloides Bge. (Fam. Liliaceae). It has been demonstrated to have a good anti‐inflammatory effect and a low bioavailability (1.1%). Clinical research has focused on developing it into a completely new medicine. In this study, a rapid and sensitive analytical method based on LC‐MS/MS has been developed for the determination of TB‐II in rat biological matrices (tissues, bile, urine and feces samples). The analytes and internal standard were isolated from 100 μL samples by solid‐phase extraction and then separated using a DIKMA Inertsil ODS‐3 column (5 µm, 2.1 × 150 mm) with an isocratic mobile phase consisting of acetonitrile–0.05% formic acid (35:65) at a flow rate of 0.25 mL/min. Calibration curves (1/χ²‐weighted) offered satisfactory linearity (r² ≥ 0.990) within the test range. The accuracy, precision, recoveries and matrix effects were satisfactory in all the biological matrices examined. The assay was successfully applied to a tissue distribution and excretion study in rats. The preclinical data are useful for the design of clinical trials of TB‐II. Copyright © 2013 John Wiley & Sons, Ltd.     

Development of a multi‐mycotoxin liquid chromatography/tandem mass spectrometry method for sweet pepper analysis

A multi‐mycotoxin method was developed for the simultaneous determination of trichothecenes (nivalenol, deoxynivalenol, 3‐acetyldeoxynivalenol, 15‐acetyldeoxynivalenol, neosolaniol, fusarenon‐X, diacetoxyscirpenol, HT‐2 toxin, T‐2 toxin), aflatoxins (aflatoxin‐B₁, aflatoxin‐B₂, aflatoxin‐G₁ and aflatoxin‐G₂), Alternaria toxins (alternariol, alternariol methyl ether and altenuene), fumonisins (fumonisin‐B₁, fumonisin‐B₂ and fumonisin‐B₃), ochratoxin A, zearalenone, beauvericin and sterigmatocystin in sweet pepper. Sweet pepper was extracted with ethyl acetate/formic acid (99:1, v/v). After splitting up the extract, two‐thirds of the extract was cleaned up using an aminopropyl column followed by an octadecyl column. The remaining part was cleaned up using a strong anion‐exchange column. After recombination of both cleaned parts of the sample extract, the combined solvents were evaporated and the residue was dissolved in mobile phase; 20 µL was injected into the chromatographic system, so only one run was used to separate and detect the mycotoxins in positive electrospray ionization using selected reaction monitoring. The samples were analyzed with a Micromass Quattro Micro triple quadrupole mass spectrometer (Waters, Milford, MA, USA). The mobile phase consisted of variable mixtures of water and methanol, 1% acetic acid and 5 mM ammonium acetate. The limits of detection of the multi‐mycotoxin method varied from 0.32 µg.kg^?1 to 42.48 µg.kg^?1. The multi‐mycotoxin liquid chromatography/tandem mass spectrometry (LC/MS/MS) method fulfilled the method performance criteria required by the Commission Regulation (EC) No 401/2006. Sweet peppers inoculated by Fusarium species were analyzed using the developed method. Beauvericin (9–484 µg.kg^?1) and fumonisins (fumonisin‐B₁ up to 4330 µg.kg^?1, fumonisin‐B₂ up to 4900 µg.kg^?1, and fumonisin‐B₃ up to 299 µg.kg^?1) were detected. Copyright © 2008 John Wiley & Sons, Ltd.     

An LC–MS/MS method for the quantification of diclofenac sodium in dairy cow plasma and its application in pharmacokinetics studies

An LC–MS/MS method with internal standard tolfenamic acid for determining diclofenac sodium (DCF) in dairy cow plasma was developed and validated. Samples were processed with protein precipitation by cold formic acid–acetonitrile. Determination of DCF was performed using LC–ESI⁺–MS/MS with the matrix‐matched calibration curve. The results showed that the method was sensitive (LOD 2 ng mL^?1, LOQ 5 ng mL^?1), accurate (97.60 ± 5.64%), precise (<10%) and linear in the range of 5–10,000 ng mL^?1. A single intravenous (i.v.) or intramuscular (i.m.) administration of 5% diclofenac sodium injection at a dose of 2.2 mg kg^?1 was performed in six healthy dairy cows according to a two‐period crossover design. The main pharmacokinetic (PK) parameters after a single i.v. administration were as follows: t_1/2β, 4.52 ± 1.71 h; AUC, 77.79 ± 16.76 h μg mL^?1; mean residence time, 5.16 ± 1.11 h. The main PK parameters after a single i.m. administration were as follows: T_max, 2.38 ± 1.19 h; C_max, 7.46 ± 1.85 μg mL^?1; t_1/2β, 9.46 ± 2.86 h; AUC 67.57 ± 13.07 h μg mL^?1. The absolute bioavailability was 87.37 ± 5.96%. The results showed that the diclofenac sodium injection had PK characteristics of rapid absorption and slow elimination, and high peak concentration and bioavailability in dairy cows, and that the recommended clinical dosage of diclofenac sodium injection is 2.2 mg kg^?1.     

Design,Synthesis and Biological Evaluation of Novel N‐(4‐([2,2′:5′,2′′‐Terthiophen]‐5‐yl)‐2‐methylbut‐3‐yn‐2‐yl) Benzamide Derivatives

On the basis of the principle of combination of active groups, a series of novel N‐(4‐([2,2′:5′,2′′‐terthiophen]‐5‐yl)‐2‐methylbut‐3‐yn‐2‐yl) benzamide derivatives were designed, synthesized and systematically evaluated for their antiviral activity against tobacco mosaic virus (TMV). The bioassay results showed that most of these compounds displayed good anti‐TMV activity, and some of them exhibited higher antiviral activity than commercial Ningnanmycin. Especially, compound 8e with excellent anti‐TMV activity (inactivation activity, 92.3%/500 µg·mL^?1; curative activity, 85.7%/500 µg·mL^?1 and protection activity, 64.7%/500 µg·mL^?1) emerged as a potential inhibitor of plant virus TMV. Quantitative structure‐activity relationship studies proved that the van der Waals volume (V) and electronic parameter (∑(∑σ_o+σ_p) and ∑σ_m) for the substituent R¹ were very important for antiviral activities in this class of compounds.     

Malva sylvestris L. extract suppresses desferrioxamine‐induced PGE2 and PGD2 release in differentiated U937 cells: the development and validation of an LC‐MS/MS method for prostaglandin quantification

Malva sylvestris is a species used worldwide as an alternative to anti‐inflammatory therapies; however, its mechanism of action remains unknown. In this paper, the anti‐inflammatory effects of M. sylvestris alcoholic extracts were evaluated by measuring the pro‐inflammatory mediators PGE₂ and PGD₂ in desferrioxamine‐stimulated phorbol 12‐myristate 13‐acetate‐differentiated U937 cells. An HPLC‐DAD fingerprint of the M. sylvestris extract was performed and caffeic acid, ferulic acid and scopoletin were identified and quantified. An HPLC‐MS/MS method was developed and validated to separate and measure the prostaglandins. The lower limits of detection (~0.5 ng/mL for PGE₂ and PGD₂) and quantification (1.0 ng/mL for PGE₂ and PGD₂) indicated that the method is highly sensitive. The calibration curves showed excellent coefficients of correlation (r > 0.99) over the range of 1.0–500.0 ng/mL, and at different levels, the accuracy ranged from 96.4 to 106.4% with an RSD < 10.0% for the precision study. This method was successfully applied using U937‐d cells. A significant dose‐dependent reduction of PGE₂ and PGD₂ levels occurred using 10 µg/mL (10.74 ± 2.86 and 9.60 ± 6.89%) and 50 µg/mL of extract (48.37 ± 3.24 and 53.06 ± 6.15%), suggesting that the anti‐inflammatory mechanisms evoked by M. sylvestris may be related to modulation of these mediators. Copyright © 2014 John Wiley & Sons, Ltd.     

Synthetic and antimicrobial studies on new gold(I) complexes of imidazolidin‐2‐ylidenes

Six new 1,3‐diorganylimidazolidin‐2‐ylidene (NHC) gold(I) complexes of the type [Au(NHC)₂]⁺ (1–6), were synthesized by reacting [AuCl(PPh)₃] with 1,3‐dimesitylimidazolidin‐2‐ylidene or bis(1,3‐dialkylimidazolidin‐2‐ylidene). The complexes 1–6 were fully characterized by elemental analyses and spectroscopic data. The placement of mesityl or para‐substituted benzyl groups on the nitrogen atoms of the ring of the complexes leads to the particularly active antibacterial agents evaluated in this work. It is worth noting that the p‐methoxybenzyl derivative (2) inhibited the growth of Pseudomona aeruginosa, Staphylococcus epidermidis, Staphylococcus aureus and Enterococcus faecalis with minimum inhibitory concentration (MIC) values of 3.12 µg ml^?1, 6.25 µg ml^?1, 3.12 µg ml^?1 and 3.12 µg ml^?1 respectively. In contrast, the analogous p‐dimethylaminobenzyl derivative (3) is effective only against Escherichia coli (MIC = 3.12 µg ml^?1). Copyright © 2004 John Wiley & Sons, Ltd.     

OH‐Initiated Photooxidations of 1‐Pentene and 2‐Methyl‐2‐propen‐1‐ol: Mechanism and Yields of the Primary Carbonyl Products

The products of the gas‐phase reactions of OH radicals with 1‐pentene and 2‐methyl‐2‐propen‐1‐ol (221MPO) at T=298±2 K and atmospheric pressure were investigated by using a 4500 L atmospheric simulation chamber that was built especially for this work. The molar yield of butyraldehyde was 0.74±0.12 mol for the reaction of 1‐pentene. This work provides the first product molar yield determination of formaldehyde (0.82±0.12 mol), 1‐hydroxypropan‐2‐one (0.84±0.13 mol), and methacrolein (0.078±0.012 mol) from the reaction of 221MPO with OH radicals. The mechanism of this reaction is discussed in relation to the experimental results. Additionally, taking into consideration the complex mechanism, the rate coefficients of the reactions of OH with formaldehyde, 1‐hydroxypropan‐2‐one, and methacrolein were derived at atmospheric pressure and T=298±2 K.; the obtained values were (8.9±1.6)×10^?12, (2.4±1.4)×10^?12, and (22.9±2.3)×10^?12 cm³ molecule^?1 s^?1, respectively.     

Determination of a hydrophilic paclitaxel derivative, 7‐xylosyl‐10‐deacetylpaclitaxel in rat plasma by LC–MS/MS

A LC‐MS/MS method for the determination of a hydrophilic paclitaxel derivative 7‐xylosyl‐10‐deacetylpaclitaxel in rat plasma was developed to evaluate the pharmacokinetics of 7‐xylosyl‐10‐deacetylpaclitaxel in the rats. 7‐Xylosyl‐10‐deacetylpaclitaxel and docetaxel (IS for 7‐xylosyl‐10‐deacetylpaclitaxel) were extracted from rat plasma with acetic ether and analyzed on a Hypersil C₁₈ column (4.6 × 150 mm i.d., particle size 5 µm) with the mobile phase of ACN/0.05% formic acid (50:50, v/v). The analytes were detected using an ESI MS/MS in the multiple reaction monitoring mode. The standard curves for 7‐xylosyl‐10‐deacetylpaclitaxel in plasma were linear (r >0.999) over the concentration range of 2.0–1000 ng/mL with a weighting of 1/concentration². The method showed a satisfactory sensitivity (2.0 ng/mL using 50 µL plasma), precision (CV ≤ 10.1%), accuracy (relative error ?12.4 to 12.0%), and selectivity. This method was successfully applied to the pharmacokinetic study of 7‐xylosyl‐10‐deacetylpaclitaxel in rat plasma after intravenous administration of 7‐xylosyl‐10‐deacetylpaclitaxel to female Wistar rats. Copyright © 2008 John Wiley & Sons, Ltd.     

Relative tissue distribution and excretion studies of gastrodin and parishin from powder and extract of Gastrodiae Rhizoma in rat by UHPLC‐ESI‐MS/MS

New research has indicated that Gastrodiae Rhizome (GR) has potential anti‐diabetic and anti‐asthmatic effects in mouse models. On the basis of our previous study of the relative bioavailability of gastrodin (GAS) and parishin (PA) from extract and powder of GR, we performed further research on the tissue distribution and excretion of the two analytes. A reliable bioanalytical method for the quantification of GAS and PA in rat tissues and excretion is required. Chromatographic separation was carried out on a gradient mobile phase of acetonitrile–water with 0.1% formic acid. Calibration curves (1/x ² weighted) offered satisfactory linearity (r ² > 0.9835) within 100–3000 ng mL⁻¹ for GAS and (r ² > 0.9862) within 10–1000 ng mL⁻¹ for PA. The relative standard deviations of the intra‐day and inter‐day precision were all <14.98%, whilst the relative errors of the intra‐day and inter‐day accuracy were all within ±14.71%. The matrix effect and recovery values were satisfactory in all of the biological matrices examination. The data of relative differences in tissue distribution and excretion of GAS and PA from powder and extract of GR indicated that higher bioavailabilities for GAS and PA were obtained when a dosage of 4 g kg⁻¹ GR powder was used.     

Quantification of ginsenosides Rh4 and Rk3 in rat plasma by liquid chromatography‐tandem mass spectrometry: Application to a pre‐clinical pharmacokinetic study

Ginsenoside Rh4 (Rh4) and ginsenoside Rk3 (Rk3) are two active substances isolated from the processed Panax species. To further explore their potential medicinal application, a reliable liquid chromatography‐tandem mass spectrometry method (LC/MS/MS) was developed and validated for the quantification of Rh4 and Rk3 in rat plasma. Multiple ion monitoring and multiple reaction monitoring experiments were performed in negative ionization mode. This LC/MS/MS method had good selectivity, sensitivity (lower limit of quantification = 10 ng/mL), precision (intra‐ and inter‐day relative standard deviation ≤ 10.1) and accuracy (analytical recovery within 100 ± 10%). The pharmacokinetic profiles of Rh4 and Rk3 were subsequently assessed in Sprague–Dawley rats. Similar to many other ginsenosides, the oral bioavailability of Rh4 and Rk3 was unfavorable, and Rh4 and Rk3 did not have any measurable plasma exposure after oral administration (20 mg/kg). Fortunately, upon intravenous administration (5 mg/kg), both Rh4 and Rk3 possessed abundant plasma exposure, moderate clearance (Cl = 50.2 ± 7.7 and 23.8 ± 1.4 mL·min^?1·kg^?1, respectively) and terminal elimination half‐life (t_{1/2 λZ} = 157.2 ± 65.2 and 99.5 ± 37.8 min, respectively). As Rh4 and Rk3 displayed favorable intravenous pharmacokinetic profiles, further exploration on their medicinal application is warranted. Copyright © 2012 John Wiley & Sons, Ltd.     

Liquid chromatography–mass spectrometry for the simultaneous determination of the catalpol‐related iridoid glucosides,verproside, isovanilloylcatalpol,catalposide and 6‐O‐veratroyl catalpol in rat plasma

Verproside, isovanilloylcatalpol, catalposide and 6‐O‐veratroyl catalpol are bioactive iridoid glucosides isolated from in a number of folk medicinal plants. A rapid, sensitive and selective liquid chromatography/mass spectrometric (LC/MS) method for the simultaneous determination of verproside, isovanilloylcatalpol, catalposide and 6‐O‐veratroyl catalpol in rat plasma was developed. The analytes were extracted from 50 µL of rat plasma with ethyl acetate using 7‐carboxymethyloxy‐3',4',5‐trimethoxyflavone as internal standard and analyzed on an X‐Bridge C₁₈ column within 6.5 min with 40% methanol in 10 mm ammonium formate (pH 3.0). The analytes were quantified using an electrospray ionization mass spectrometry in the selected ion monitoring mode. The standard curves were linear over the concentration ranges of 10–2000 ng/mL for verproside, isovanilloylcatalpol and catalposide and 20–2000 ng/mL for 6‐O‐veratroyl catalpol. The coefficients of variation and relative errors of verproside, isovanilloylcatalpol, catalposide and 6‐O‐veratroyl catalpol for intra‐ and inter‐assay at four quality control levels were 2.5–8.0 and–4.0–6.6%, respectively. This method was successfully applied to the pharmacokinetic study of verproside and its possible metabolite isovanilloylcatalpol after intravenous administration of verproside, a candidate anti‐asthma drug, in male Sprague–Dawley rats. Copyright © 2009 John Wiley & Sons, Ltd.     

Preparation,Characterization and Electrochemical Application of Graphene‐metallic Nanocomposites

Three different Graphene‐Metallic (Graphene‐Me) nanocomposites – Graphene‐Silver (Graphene‐Ag), Graphene‐Gold (Graphene‐Au) and Graphene‐Platinum (Graphene‐Pt) nanocomposites – were prepared and characterized. The electrochemical performances of these nanocomposites were tested by incorporating them with glassy carbon paste electrode (GCPE) and used them in biofuel cells (BFC) and as amperometric xanthine biosensor transducers. Present work contains the first application of Graphene‐Au and Graphene‐Ag nanocomposite in BFCs and also first application of these Graphene‐Me nanocomposites in xanthine biosensors. Considering BFC, power and current densities were calculated as 2.03 µW cm^?2 and 167.46 µA cm^?2 for the plain BFC, 3.39 µW cm^?2 and 182.53 µA cm^?2 for Graphene‐Ag, 4.43 µW cm^?2 and 230.15 µA cm^?2 for Grapehene‐Au and 6.23 µW cm^?2 and 295.23 µA cm^?2 for Graphene‐Pt nanocomposite included BFCs respectively. For the amperometric xanthine biosensor linear ranges were obtained in the concentration range between 5 µM and 50 µM with the RSD (n=3 for 30 µM xanthine) value of 4.28 % for plain xanthine biosensor, 3 µM and 50 µM with the RSD (n=3 for 30 µM xanthine) value of 9.37 % for Graphene‐Ag, 5 µM to 20 µM with the RSD (n=3 for 5 µM xanthine) value of 9.00 % and 30 µM to 70 µM with the RSD (n=3 for 30 µM xanthine) value of 8.80 % for Grapehene‐Au and 1 µM and 70 with the the RSD (n=3 for 30 µM xanthine) value of 2.59 % for Grapehene‐Pt based xanthine biosensors respectively.     

A Highly Selective and Sensitive Fluorescent Probe Recognition for Co2+ in Aqueous Media Based on 8‐Hydroxyquinolin‐2‐carbaldehyde‐2‐pyridylformylhydrazone Derivative

A new (8‐hydroxyquinolin‐2‐yl)methylene picolinohydrazide derivative ( L ) has been successfully synthesized and characterized. The probe L displays high selectivity to Co²⁺ in CH₃CN/HEPES (1:1, Ｖ/Ｖ, 10 mmol·L^?1, pH=7.4) with a fluorescence "ON‐OFF" response. The Co²⁺ ion recognition event possesses some distinct features including rapid response, high selectivity and sensitivity, good anti‐interference ability and being applicable within a wide pH range. Based on job's plot and ESI‐MS studies, the 1:1 binding mode was proposed. The binding constant of L and Co²⁺ is 1.63×10⁸ L·mol^?1 and the detection limit is 1.15 µmol·L^?1. Natural water samples experiments revealed that probe L can be potentially applied to the detection of Co²⁺ in real environment.     

LC‐MS/MS methods for the determination of edaravone and/or taurine in rat plasma and its application to a pharmacokinetic study

Three liquid chromatography–tandem mass spectrometry (LC‐MS/MS) methods were respectively developed and validated for the simultaneous or independent determination of taurine and edaravone in rat plasma using 3‐methyl‐1‐p‐tolyl‐5‐pyrazolone and sulfanilic acid as the internal standards (IS). Chromatographic separations were achieved on an Agilent Zorbax SB‐Aq (100 × 2.1 mm, 3.5 µm) column. Gradient 0.03% formic acid–methanol, isocratic 0.1% formic acid–methanol (90:10) and 0.02% formic acid–methanol (40:60) were respectively selected as the mobile phase for the simultaneous determination of two analytes, taurine or edaravone alone. The MS acquisition was performed in multiple reaction monitoring mode with a positive and negative electrospray ionization source. The mass transitions monitored were m/z [M + H]⁺ 175.1 → 133.0 and [M + H]⁺ 189.2 → 147.0 for edaravone and its IS, m/z [M ? H]^? 124.1 → 80.0 and [M ? H]^? 172.0 → 80.0 for taurine and its IS, respectively. The validated methods were successfully applied to study the pharmacokinetic interaction of taurine and edaravone in rats after independent intravenous administration and co‐administration with a single dose. Our collective results showed that there were no significant alterations on the main pharmacokinetic parameters (area under concentration–time curve, mean residence time, half‐life and clearance) of taurine and edaravone, implying that the proposed combination therapy was pharmacologically feasible. Copyright © 2014 John Wiley & Sons, Ltd.     

Dual‐column capillary microextraction (CME) combined with electrothermal vaporization inductively coupled plasma mass spectrometry (ETV‐ICP‐MS) for the speciation of arsenic in human hair extracts

In this work, dual‐column capillary microextraction (CME) system consisting of N‐(2‐aminoethyl)‐3‐aminopropyltrimethoxysilane (AAPTS)‐silica coated capillary (C1) and 3‐mercaptopropyl trimethoxysilane (MPTS)‐silica coated capillary (C2) was developed for sequential separation/preconcentration of arsenite [As(III)], arsenate [As(V)], monomethylarsonic acid [MMA(V)] and dimethylarsinic acid [DMA(V)] in the extracts of human hair followed by electrothermal vaporization inductively coupled plasma mass spectrometry (ETV‐ICP‐MS) detection with iridium as permanent modifier. Various experimental parameters affecting the dual‐column microextraction of different As species had been investigated in detail. It was found that at pH 9, As(V) and MMA could be quantitatively retained by C1 and only As(III) could be quantitatively retained by C2. With the aid of valve switching, As(V)/MMA(V) retained on C1 and As(III) retained on C2 could be sequentially desorbed by 10 µl of 0.01 mol l^?1 HNO₃ [for As(V)], 0.1 mol l^?1 HNO₃ [for MMA(V)] and 0.2 mol l^?1 HNO₃‐3% thiourea (m/v) [for As(III)], respectively, the eluents were immediately introduced into the Ir‐coated graphite tubes for further ETV‐ICP‐MS detection. With two‐step ETV pyrolysis program, Cl^? in the sample matrix could be in situ removed, and the total As in the human hair extracts or digested solution could be interference‐free, determined by ETV‐ICP‐MS. DMA(V) in the human hair extracts was obtained by subtraction of total As in the human hair extracts from other three As species. Under the optimized conditions, the detection limits (3 σ) of the method were 3.9 pg ml^?1 for As(III), 2.7 pg ml^?1 for As(V), 2.6 pg ml^?1 for MMA(V) and 124 pg ml^?1 for total As with the relative standard deviations less than 7.0% (C = 0.1 ng ml^?1, n = 7), and the enrichment factor was 286, 262 and 260 for As(III), As(V) and MMA(V), respectively. The developed method was successfully applied for the speciation of arsenic in the extracts of human hair. Copyright © 2009 John Wiley & Sons, Ltd.     

Quantification issues of trace metals analysis on silicon oxide and nitride films by using VPD‐ICP‐MS and VPD‐GF‐AAS

Vapor phase decomposition (VPD) is a pretreatment technique for collecting trace metal contaminants on the surface of a Si wafer. Such trace metals can be identified and quantified by inductively coupled plasma mass spectrometry (ICP‐MS) or graphite furnace atomic absorption spectroscopy (GF‐AAS). However, the analytical results can be influenced by the Si‐matrix in the VPD samples. This article discusses the approaches to eliminate the interference caused by Si‐matrix. When the thickness of oxide film on wafer surface is less than 100 Å, the quantification results of ICP‐MS analysis will not be affected by Si‐matrix in the VPD samples. Except this, the Si‐matrix must be removed before analysis. An improved heating pretreatment approach has been adopted successfully to eliminate the Si‐matrix. For GF‐AAS analysis, the Si‐matrix will influence the sodium and aluminum analyses. Adding HNO₃ to the graphite furnace tubing after sample injection could also eliminate the interference caused by the Si‐matrix. The method detection limits (MDLs) of VPD‐GF‐AAS and VPD‐ICP‐MS range from 0.04 to 0.55 × 10¹⁰ atoms cm^?2 and 0.05 to 1.73 × 10⁹ atoms cm^?2, respectively. Copyright © 2008 John Wiley & Sons, Ltd.     

Rapid structural characterization of in vivo and in vitro metabolites of tinoridine using UHPLC–QTOF–MS/MS and in silico toxicological screening of its metabolites

Tinoridine is a nonsteroidal anti‐inflammatory drug and also has potent radical scavenger and antiperoxidative activity. However, metabolism of tinoridine has not been thoroughly investigated. To identify in vivo metabolites, the drug was administered to Sprague–Dawley rats (n = 5) at a dose of 20 mg kg^?1, and blood, urine and feces were collected at different time points up to 24 h. In vitro metabolism was delved by incubating the drug with rat liver microsomes and human liver microsomes. The metabolites were enriched by optimized sample preparation involving protein precipitation using acetonitrile, followed by solid‐phase extraction. Data processes were carried out using multiple mass defects filters to eliminate false‐positive ions. A total of 11 metabolites have been identified in urine samples including hydroxyl, dealkylated, acetylated and glucuronide metabolites; among them, some were also observed in plasma and feces samples. Only two major metabolites were formed using liver microsomal incubations. These metabolites were also observed in vivo. All the 11 metabolites, which are hitherto unknown and novel, were characterized by using ultrahigh‐performance liquid chromatography–quadrupole time‐of‐flight tandem mass spectrometry in combination with accurate mass measurements. Finally, in silico toxicological screening of all metabolites was evaluated, and two metabolites were proposed to show a certain degree of lung or liver toxicity. Copyright © 2015 John Wiley & Sons, Ltd.     

Synthesis and Anti‐tumor Evaluation of Novel C‐37 Modified Derivatives of Gambogic Acid

Gambogic acid (GA, 1 ), the most prominent representative of Garcinia natural products, has been reported to be a promising anti‐tumor agent. In order to further explore the structure‐activity relationship of GA and discover novel GA derivatives as anti‐tumor agents, 17 novel C‐37 modified derivatives of GA were synthesized and evaluated for their in vitro anti‐tumor activities against A549, HCT‐116, BGC‐823, HepG2 and MCF‐7 cancer cell lines. Among them, 11 compounds were found to be more potent than GA against some cancer cell lines. Notably, compound 8 was almost 5–10 folds more active than GA against A549 and BGC‐823 cell lines with the IC₅₀ values of 0.12 µmol·L^?1 and 0.57 µmol·L^?1, respectively. Chemical modification at C‐37 position of GA by introducing of hydrophilic amines could lead to increased activity and improved drug‐like properties. These findings will enhance our understanding of the structure‐activity relationship (SAR) of GA and lead to the discovery of novel GA derivatives as potential anti‐tumor agents.