Evaluation of statistical control charts for on-line radiation monitoring

Statistical control charts are presented for the evaluation of time series radiation counter data from flow cells used for monitoring of low levels of ⁹⁹TcO₄⁻ in environmental solutions. Control chart methods consisted of the 3-sigma (3σ) chart, the cumulative sum (CUSUM) chart, and the exponentially weighted moving average (EWMA) chart. Each method involves a control limit based on the detector background which constitutes the detection limit. Both the CUSUM and EWMA charts are suitable to detect and estimate sample concentration requiring less solution volume than when using a 3σ control chart. Data presented here indicate that the overall accuracy and precision of the CUSUM method is the best.     

Relation between the thermal behavior of polyacrylonitrile and polymerization factors

In order to clarify the mechanism to produce the large dispersion of the exothermic peak temperature (T_pk) of polyacrylonitrile, a systematic and quantitative study was made by means of the differential thermal analysis and the viscosity measurment. General tendency between T_pk and the polymerization methods was reconfirmed. Under a controlled condition (i.e., aqueous solution system), presence of N,N-dimethyl formamide or isopropyl alcohol produced a lower T_pk of resulting polymer, while presence of activator produced a higher T_pk. Thus, the large dispersion of T_pk (250–300°C) can be explained inclusively in terms of a single reaction factor, i.e., chain transfer mechanism. Particularly in the above third case it was shown that owing to strong and rapid chain transfer to activator, some kind of secondary reaction (caused by propagating chain end radical), probably chain branching which deteriorates the higher thermal quantity of molecule, is restrained effectively. Furthermore, some specific behaviors (i.e., cooperativeness and dynamic character, etc.) were observed in this reaction of PAN in solid amorphous phase.     

Practical aspects concerning validation and quality control for forensic and clinical bioanalytical quantitative methods

Reporting reliable analytical data is the backbone of forensic and clinical bioanalytical research and applications. Therefore, international agreement concerning validation and quality control requirements is needed. Several international guidelines provide a standard for fundamental validation parameters such as selectivity, matrix effects, method limits, calibration, accuracy, precision and stability. However, it is not always easy for the analyst to ‘translate’ these guidelines into practice. International guidelines remain nonbinding protocols that need to be updated according to the type of application and the analyst’s method requirements and depends on the evolution of analytical techniques. In this publication, suggestions for experimental set-up, statistical approaches and straightforward acceptance criteria for validation of forensic bioanalytical applications are suggested. Furthermore, permanent quality control, to ensure state-of-the-art quantitative analytical performances, as well as measurement uncertainty influencing interpretation is discussed.     

Characterization of imatinib mesylate formulations distributed in South American countries: Determination of genotoxic impurities by UHPLC–MS/MS and dissolution profile

Imatinib mesylate (IM) is an anti‐neoplasic drug used for the treatment of cancer. Recent new guidelines specify daily doses and concentration limits for genotoxic impurities (GTIs) in pharmaceutical final products. Therefore, in this work an analytical method using UHPLC–MS/MS was developed, validated and applied to characterize IM tablets for two GTIs: N‐(2‐methyl‐5‐aminophenyl)‐4‐(3‐pyridyl)‐2‐pyrimidine amine (Imp. 1), and N‐[4‐methyl‐3‐(4‐methyl‐3‐yl‐pyrimidin‐2‐ylamino)‐phenyl]‐4‐ chloromethyl benzamide (Imp. 2), simultaneously. Additionally, dissolution data of IM tablets were compared using a methodology recommended by the US Food and Drug Administration. The UHPLC method utilized an Acquity BEH C₁₈ (150 × 2.1 mm, 1.7 μm) maintained at 40°C. The mobile phase consisted of ammonium formate 0.063% (phase A) and acetonitrile plus 0.05% formic acid (phase B) in gradient elution. A sensitive method for determination of previously mentioned GTIs in IM tablets was successfully developed and applied. Overall, the formulations analyzed in this work showed low levels of Imp. 1 and Imp. 2. However, the sample named D1 showed very high levels of Imp. 1 and failed to meet the requirements established by the US Food and Drug Administration for dissolution data. Periodic verification of GTIs in pharmaceutical formulations is important to minimize safety risks, so analytical methods to determine it need be available and implemented in routine analysis.     

m‐Methoxy Substituents in a Tetraphenylethylene‐Based Hole‐Transport Material for Efficient Perovskite Solar Cells

Three tetrapheynlethylene derivatives (N,N‐di(4‐methoxyphenyl)aminophenyl‐substituted tetraphenylethylene; TPE‐4DPA) with different methoxy positions (pp‐, pm‐, and po‐) have been synthesized and characterized. The methoxy groups can control the oxidation potential of the materials, and the electronic properties of the derivatives were affected by the position of the methoxy substituents. These compounds were synthesized in a facile and cost‐effective way, and were applied as hole‐transport materials in perovskite solar cells. The corresponding cell performances were compared with respect to their structure modifications, and it was found that the derivative with m‐OMe substituents showed the highest power conversion efficiency (PCE) of 15.4 %, with a J_sc value of 20.04 mA cm^?2, a V_oc value of 1.07 V, and a fill factor (FF) value of 0.72, which is higher than the p‐OMe and o‐OMe substituents. Moreover, the PCE of pm‐TPE‐4DPA is comparable with that of the state‐of‐the‐art 2,2′,7,7′‐tetrakis(N,N′‐di‐p‐methoxyphenylamine)‐9,9′‐spirobifluorene under identical conditions.     

Determination of quinocide as impurity in primaquine tablets by capillary zone electrophoresis

A capillary zone electrophoretic method has been developed and validated for the determination of the impurity quinocide (QC) in the antimalarial drug primaquine (PQ). Different buffer additives such as native cyclodextrins and crown ethers were evaluated. Promising results were obtained when either β‐cyclodextrin (β‐CD) or 18‐crown‐6 ether (18C6) were used. Their separation conditions such as type of buffer and its pH, buffer additive concentration, applied voltage capillary temperature and injection time were optimized. The use of 18C6 offers slight advantages over β‐CD such as faster elution times and improved resolution. Nevertheless, migration times of less than 5 min and resolution factors (R_s) in the range of 2–4 were obtained when both additives were used. The method was validated with respect to selectivity, linearity, limits of detection and quantitation, analytical precision (intra‐ and inter‐day variability) and repeatability. Concentrations of 2.12 and 2.71% (w/w) of QC were found in pharmaceutical preparations of PQ from two different manufacturers. A possible mechanism for the successful separation of the isomers is also discussed. Copyright © 2008 John Wiley & Sons, Ltd.     

Analytical method for urinary metabolites as biomarkers for monitoring exposure to phthalates by gas chromatography/mass spectrometry

Phthalates, widely used as plasticizers, have been detected in indoor air, but there have been few reports on methods of analyzing urinary metabolites as biomarkers to monitor exposure to di‐n ‐pentyl phthalate or di‐n ‐hexyl phthalate. Presented here is a cost‐effective and sensitive analytical method for the determination of urinary metabolites of phthalates containing these two compounds. Nine urinary phthalate metabolites were enzymatically hydrolyzed and extracted with toluene: monomethyl phthalate, monoethyl phthalate, monoisobutyl phthalate, mono‐n‐ butyl phthalate, mono‐n‐ pentyl phthalate, mono‐n‐ hexyl phthalate, monocyclohexyl phthalate, monobenzyl phthalate and mono(2‐ethyl‐5‐carboxypentyl) phthalate. After transformation to their tert‐ butyldimethylsilyl derivatives, they were analyzed by gas chromatography/mass spectrometry in the electron impact ionization mode. The calibration curves for the metabolites were linear at urinary concentrations of up to 30 μg/L, showing that they could be determined accurately and precisely (detection limits 0.1–0.4 μg/L, quantification limits 0.3–1.3 μg/L). The urine samples collected could be stored for up to 1 month at −20°C. The proposed analytical method was used to examine urine samples from seven healthy volunteers. This method should be useful for monitoring phthalate exposure in the general population.     

Simultaneous determination of residues of thiamethoxam and its metabolite clothianidin in tobacco leaf and soil using liquid chromatography‐tandem mass spectrometry

A simple analytical method was developed to simultaneously determine thiamethoxam and its metabolite, clothianidin, in fresh tobacco leaf, soil and cured tobacco leaf using liquid chromatography with tandem mass spectrometry. Thiamethoxam and clothianidin in tobacco and soil samples were extracted with acetonitrile containing 0.1% formic acid and purified using an NH₂‐SPE column. The optimized method provided good linearity with coefficients of determination R² ≥ 0.9981. The limits of detection and quantification were between 0.006–0.12 and 0.02–0.4 mg/kg, respectively. Intra‐ and inter‐day recovery assays were used to validate the established method. The average recoveries of thiamethoxam and clothianidin in fresh tobacco leaf, soil and cured tobacco leaf were 75.04–100.47%, 75.86–86.40% and 89.83–99.39%, respectively. The intra‐ and inter‐day relative standard deviations were all <9%. The developed method was successfully applied for the analysis of thiamethoxam and clothianidin residues in actual tobacco and soil samples. The results indicated that the established method met the requirements for the analysis of trace amounts of thiamethoxam and clothianidin in fresh tobacco leaf, soil and cured tobacco leaf.     

In situ X-ray Powder Diffraction Study of the Reactions of CrO2 and TlPd3O4 with Hydrogen

Hydrogen is an important reducing agent for transition metal oxides, however, details on reaction pathways are often unknown. Therefore, the reduction of CrO₂ and TlPd₃O₄ was investigated by in situ X-ray powder diffraction and subsequent Rietveld analysis. CrO₂ is reduced by hydrogen gas (0.3 MPa) starting at 180 °C according to 2 CrO₂ + H₂ → 2 CrOOH. The reaction is complete at 250 °C and there are no signs for intermediates or non-stoichiometry. In nitrogen atmosphere the reaction TlPd₃O₄ → TlPd₃ + 2 O₂ occurs without intermediates in one step starting at about 670 °C. Thermal volume expansion is determined to be V(TlPd₃O₄) = 880.7(1) 10⁶ pm³ + 1.64(7) 10⁴ T pm³/K + 10.7(9) T² pm³/K² and V(TlPd₃) = 258.6(1) 10⁶ pm³ + 8.5(7) 10³ T pm³/K + 2.6(7) T² pm³/K² for 25 °C ≤ T ≤ 730 °C. The formation of β-TlPd₃H from TlPd₃O₄ in 0.3 MPa hydrogen gas at 75 °C occurs very fast. Unit cell parameters indicate the occurrence of a metastable α-TlPd₃H_≈0.2 with a hydrogen-filled ZrAl₃ type. Cubic anti-perovskite type β-TlPd₃H reacts in air to TlPd₃ with a possible hydrogen deficient intermediate β-TlPd₃H_1–x and hints for remaining hydrogen in the tetragonal ZrAl₃ type intermetallic compound. In situ methods thus give a deeper insight in the TlPd₃-O₂-H₂ system with the identification of possible candidates for interesting intermediate phases and more detailed information on thermal stabilities.     

Simultaneous determination and pharmacokinetics of five alkaloids in rat plasma by ultra high performance liquid chromatography with tandem mass spectrometry after the oral administration of Corydalis bungeana Turcz extract

Pharmacokinetic studies were conducted on rats for protopine, corynoline, 7′‐(3′,4′‐dihydroxyphenyl)‐N‐[(4‐methoxyphenyl)‐ethyl]propenamide, acetylcorynoline, and 8‐oxocorynoline, five main active components from Corydalis bungeana Turcz (C. bungeana Turcz). An ultra high performance liquid chromatography with tandem mass spectrometry method has been developed and validated for the simultaneous determination of the pharmacokinetic characteristics of these components in rat plasma. Chromatographic separation was achieved on an Agilent SB‐C₁₈ column (1.8 μm, 150 × 2.1 mm) using a gradient elution program with a mobile phase consisting of acetonitrile and water containing 0.1% acetic acid at a flow rate of 0.3 mL/min. The analytes were detected in the multiple reaction monitoring mode with positive electrospray ionization. Lower limits of quantification were >0.680 ng/mL and matrix effects ranged from 91.26 to 100.38%. The mean extraction recoveries of quality control samples were less than 79.32%, and the precision and accuracy were within the acceptable limits. All analytes were proven to be stable during sample storage and analysis procedures. The validated method was successfully applied to the pharmacokinetic study of five alkaloid components after oral administration of C. bungeana Turcz extract to rats. The obtained results may be helpful to reveal the mechanism of action and to guide the clinical application of C. bungeana Turcz.     

Ultra‐performance convergence chromatography method for the determination of four chromones and quality control of Saposhnikovia divaricata (Turcz.) Schischk.

Ultra‐performance convergence chromatography is an environmentally friendly analytical technique that employs dramatically reduced amounts of organic solvents compared to conventional chromatographic methods. In this study, a rapid, sensitive, and environmentally friendly method based on ultra‐performance convergence chromatography was developed for the quantification of four major chromones present in the roots of Saposhnikovia divaricata (Turcz.) Schischk. Using this method, the analysis time was significantly shortened compared to conventional high‐performance liquid chromatography techniques. In addition, the influence of cosolvent type, cosolvent ratio, column temperature, system pressure, and flow rate on the peak resolution was investigated. The proposed method was validated in terms of its limits of detection, limits of quantitation, linearity, precision, and accuracy. More specifically, the limits of detection of the four chromones ranged from 0.006 to 0.033 μg/mL, while the limits of quantitation ranged from 0.019 to 0.101 μg/mL. Our method also exhibited a good regression (r² > 0.999), excellent precision (RSD < 0.60%), and acceptable recoveries (99.48–102.89%). Finally, the quantities of these four chromones present in 20 commercial samples from Korea and China were successfully evaluated using the developed method, indicating that the proposed method is suitable for the rapid and accurate quality control of Saposhnikovia divaricata.     

Comparison of two ultrasound‐enhanced microextractions combined with HPLC for determining acaricides in water

An ultrasound‐enhanced in situ solvent formation microextraction has been developed first time and compared with ultrasound‐enhanced ionic‐liquid‐assisted dispersive liquid–liquid microextraction for the HPLC analysis of acaricides in environmental water samples. A ionic liquid ([C₈MIM][PF₆]) was used as the green extraction solvent through two pathways. The experimental parameters, such as the type and volume of both of the extraction solvent disperser solvent, ultrasonication time, and salt addition, were investigated and optimized. The analytical performance using the optimized conditions proved the feasibility of the developed methods for the quantitation of trace levels of acaricides by obtaining limits of detection that range from 0.54 to 3.68 μg/L. The in situ solvent formation microextraction method possesses more positive characteristics than the ionic‐liquid‐assisted dispersive liquid–liquid microextraction method (except for spirodiclofen determination) when comparing the validation parameters. Both methods were successfully applied to determining acaricides in real water samples.     

Simultaneous determination of ginkgolides A,B, C and bilobalide by LC‐MS/MS and its application to a pharmacokinetic study in rats

The study of pharmacokinetics of Ginkgo biloba extracts in Traditional Chinese Medicine was relatively recent. In this study, a simple, quick and sensitive LC‐MS/MS analytical method was developed for the determination of ginkgolides A, B, C and bilobalide in rat plasma. The analytes were completely separated from the endogenous compounds on an Agilent Zorbax Eclipse plus C₁₈ column (50 mm × 3.0 mm, 1.8 µm) using an isocratic elution. The single‐run analysis time was as short as 5.0 min. Sample preparation for protein removal was accomplished used a simple methanol precipitation method, after SPE showing a simultaneous extraction and cleanup of extracts allowing for a direct analysis. Extraction recoveries in rat plasma for ginkgolides A, B, C and bilobalide ranged from 75.6% to 89.0%. The calibration curves were determined over the ranges 0.5–20,000 ng/mL for ginkgolides A, B, C and bilobalide respectively. The lower limits of quantification (LLOQ) of the analytes were 0.5 ng/mL. Inter‐day and intra‐day precision and accuracy were below 15% and between 85 and 115%, respectively. Finally, the developed method was successfully applied to a pharmacokinetic study following oral administration of the Ginkgo biloba extracts to the male ICR rats. Copyright © 2015 John Wiley & Sons, Ltd.     

Membrane permeation continuous‐flow isotope ratio mass spectrometry for on‐line carbon isotope ratio determination

Gaseous membrane permeation (MP) technologies have been combined with continuous‐flow isotope ratio mass spectrometry for on‐line δ¹³C measurements. The experimental setup of membrane permeation‐gas chromatography/combustion/isotope ratio mass spectrometry (MP‐GC/C/IRMS) quantitatively traps gas streams in membrane permeation experiments under steady‐state conditions and performs on‐line gas transfer into a GC/C/IRMS system. A commercial polydimethylsiloxane (PDMS) membrane sheet was used for the experiments. Laboratory tests using CO₂ demonstrate that the whole process does not fractionate the C isotopes of CO₂. Moreover, the δ¹³C values of CO₂ permeated on‐line give the same isotopic results as off‐line static dual‐inlet IRMS δ¹³C measurements. Formaldehyde generated from aqueous formaldehyde solutions has also been used as the feed gas for permeation experiments and on‐line δ¹³C determination. The feed‐formaldehyde δ¹³C value was pre‐determined by sampling the headspace of the thermostated aqueous formaldehyde solution. Comparison of the results obtained by headspace with those from direct aqueous formaldehyde injection confirms that the headspace sampling does not generate isotopic fractionation, but the permeated formaldehyde analyzed on‐line yields a ¹³C enrichment relative to the feed δ¹³C value, the isotopic fractionation being 1.0026 ± 0.0003. The δ¹³C values have been normalized using an adapted two‐point isotopic calibration for δ¹³C values ranging from ?42 to ?10‰. The MP‐GC/C/IRMS system allows the δ¹³C determination of formaldehyde without chemical derivatization or additional analytical imprecision. Copyright © 2009 John Wiley & Sons, Ltd.     

Chemical fingerprint analysis and quantitative determination of steroidal compounds from Dioscorea villosa,Dioscorea species and dietary supplements using UHPLC‐ELSD

Ultra high‐performance liquid chromatography (UHPLC) with evaporative light scattering detection was used for the quantification of steroidal saponins and diosgenin from the rhizomes or tubers of various Dioscorea species and dietary supplements that were purported to contain Dioscorea. The analysis was performed on an Acquity UPLC? system with an UPLC? BEH Shield RP₁₈ column using a gradient elution with water and acetonitrile. Owing to their low UV absorption, the steroidal saponins were observed by evaporative light scattering detection. The 12 compounds could be separated within 15 min using the developed UHPLC method with detection limits of 5–12 µg/mL with 2 μL injection volume. The analytical method was validated for linearity, repeatability, accuracy, limits of detection and limits of quantification. The relative standard deviations for intra‐ and inter‐day experiments were <3.1%, and the recovery efficiency was 97–101%. The total content of standard compounds was found to be in the ranges 0.01–14.5% and 0.9–28.6 mg daily intake for dry plant materials and solid commercial preparations, respectively. UHPLC–mass spectrometry with a quadrupole mass analyzer and ESI source was used only for confirmation of the identity of the various saponins. The developed method is simple, rapid and especially suitable for quality control analysis of commercial products. Copyright © 2013 John Wiley & Sons, Ltd.     

M(benzo‐18‐crown‐6)I4 (M = Cd,Hg): Tetraiodide,Iodide–Iodine Adduct,or an Inclusion Compound of Iodine in MI2@(benzo‐18‐crown‐6)?

M(benzo‐18‐crown‐6)I₄ (M = Cd, Hg) are obtained as red columnar crystals from the reactions of benzo‐18‐crown‐6 (b18c6), cadmium and mercury iodide, respectively, and iodine in molar ratios of 1:1:2 in acetonitrile. They both crystallize with the orthorhombic crystal system, P2₁2₁2₁, a = 833.7(1), b = 1610.9(1), c = 1846.8(1) pm, V = 2480.3(1) 10⁶·pm³, Z = 4, for M = Cd and a = 823.4(1), b = 1616.5(1), c = 1866.1(1) pm, V = 2483.8(2) 10⁶·pm³ for M = Hg. The crystal structures consist of [M(b18c6)]I₂ molecules which are connected to a slightly lengthened iodine molecule via a secondary contact, according to the formulation I₂@[MI₂@(b18c6)].     

The Crystal Structures of Two No–Metal Tricyanomelaminates: Diammonium Tricyanomelaminate Dihydrate [NH4]2[C6N9H] · 2 H2O and Dimelaminium Tricyanomelaminate Melamine Dihydrate [C3N6H7]2[C6N9H] · C3N6H6 · 2 H2O

Diammonium tricyanomelaminate dihydrate [NH₄]₂[C₆N₉H] · 2 H₂O ( 1 ) and dimelaminium tricyanomelaminate melamine dihydrate [C₃N₆H₇]₂[C₆N₉H] · C₃N₆H₆ · 2 H₂O ( 2 ) were obtained by metathesis reactions from Na₃[C₆N₉] in aqueous solution and characterized by single‐crystal X‐ray diffraction and ¹⁵N solid‐state NMR spectroscopy ( 1 ). Both salts contain mono‐protonated tricyanomelaminate (TCM) anions and crystallize as dihydrates. Considering charge balance requirements, the crystal structure of 1 (C2/c, a = 3181.8(6) pm, b = 360.01(7) pm, c = 2190.4(4) pm, β = 112.39(3)°, V = 2319.9(8) 10⁶ · pm³) can best be described by assuming a random distribution of an ammonium ion – crystal water pair over two energetically similar sites. Apart from two melaminium cations, 2 (P2₁/c, a = 674.7(5) pm, b = 1123.6(5) pm, c = 3400.2(5) pm, β = 95.398(5), V = 2566(2) 10⁶ · pm³) contains one neutral melamine per formula unit acting as an additional “solvent” molecule and yielding a donor‐acceptor type of π–stacking interaction.     

A simple and sensitive HPLC‐UV determination of 7‐O‐succinyl macrolactin A in rat plasma and urine and its application to a pharmacokinetic study

A simple, sensitive and reproducible isocratic reversed‐phase (C₁₈) high‐performance liquid chromatography (HPLC) method was developed to determine 7‐O‐succinyl macrolactin A (SMA) in rat plasma and urine samples using UV detector set at 230 nm. Lamotrigine was used as internal standards (IS) to ensure the precision and accuracy of the method. The retention times of SMA and IS for the plasma sample were 9.2 and 4.4 min, respectively, and those for the urine samples were 7.9 and 4.3 min, respectively. The intra‐ and inter‐day variations of the analytical responses, expressed in terms of relative standard deviation, were less than 14.9%. The accuracy, in terms of average analytical recovery, ranged from 90.4 to 119%. The lower limits of quantification of SMA in rat plasma and urine samples were 0.02 and 0.1 µg/mL, respectively. This method is applicable for the pharmacokinetic studies of SMA in rats. Copyright © 2012 John Wiley & Sons, Ltd.     

Improving MCM‐41 as a Nitrosamines Trap through a One‐Pot Synthesis

Copper oxide was incorporated into MCM‐41 by a one‐pot synthesis under acidic conditions to prepare a new mesoporous nitrosamines trap for protection of the environment. The resulting composites were characterized by XRD, N₂ adsorption–desorption, and H₂ temperature‐programmed reduction techniques, and their adsorption capabilities were assessed in the gaseous adsorption of N‐nitrosopyrrolidine (NPYR). The adsorption isotherms were consistent with the Freundlich equation. The copper salt was deposited onto MCM‐41 during the evaporation stage and was fixed on the host in the calcination process that followed. MCM‐41 was able to capture NPYR in air below 373 K but not at 453 K. Loading of copper oxide on MCM‐41 greatly improved its adsorption capability at elevated temperatures. The influence of the incorporation of copper into MCM‐41 samples and the adsorption behavior of these samples are discussed in detail.     

Fast Determination of Clenbuterol and Salbutamol in Feed and Meat Products Based on Miniaturized Capillary Electrophoresis with Amperometric Detection

The fast separation capability of a novel miniaturized capillary electrophoresis with an amperometric detection (μCE‐AD) system was demonstrated by determining clenbuterol and salbutamol in real samples. The effects of several factors such as the acidity and concentration of the running buffer, the separation voltage, the applied potential and the injection time on CE‐AD were examined and optimized. Under the optimum conditions, the two β‐agonists could be baseline separated within 60 s at a separation voltage of 2 kV in a 90 mmol/L H₃BO₃‐Na₂B₄O₇ running buffer (pH 7.4), which was not interfered by ascorbic acid and uric acid. Highly linear response was obtained for above compounds over three orders of magnitude with detection limits ranging from 1.20×10^?7 to 6.50×10^?8 mol/L (S/N=3). This method was successfully used in the analysis of feed and meat products with relatively simple extraction procedures.