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Furfural and nitromethane were utilized as raw materials for the synthesis of the herbicide-safe agent Furilazole through the Henry reaction, nitro reduction and addition-cyclization-acylation. A comprehensive investigation into the involved reaction processes was conducted, leading to the identification of barium hydroxide octahydrate as the catalyst for the Henry reaction. The continuous use methodology of the excess catalyst was determined through TGA/DSC curve analysis, and a rational purification method for Henry reaction products was proposed. The nitro reduction reaction employed Pd/C catalysis, while the subsequent addition-cyclization-acylation reaction was achieved in a single step. Five impurities affecting the reaction process were identified, and their potential mechanisms of formation were postulated. Optimization of synthetic process conditions was carried out for all involved reactions. The structures of intermediates, impurities, and products were characterized using NMR, HRMS, TGA/DSC and FTIR. [ABSTRACT FROM AUTHOR]

[Objectives] To establish a HPLC-MS method for the determination of polymer impurities in cefathiamidine and its preparations. [Methods] Kromasil 100-5 C]S column (4. 6 mm x 250 mm, 5 p.m) was used for analysis; mobile phase ammonium acetate solution (pH 6. 30)-acetonitrile, gradient elution; volumetric flow rate 1.0 ml/min; column temperature 40 °C; multi-reaction monitoring mode was used for analysis, and positive ion scanning was chosen as the electrospray ion source. [Results] The resolution between impurities and main peaks under this method was greater than 1.5, and 8 known impurities and 2 polymer impurities could be completely separated and distinguished. It was inferred that the molecular ion peak [M + H] *; m/zlTl. 187 4,m/z785.193 7 was the possible polymer impurity of this product. [Conclusions] A method for the analysis of polymer impurities in cefathiamidine and its preparations was formed, which could achieve the purpose of simultaneous analysis of small molecule impurities and polymer impurities, and could better control the content of single impurities in the polymer, providing a reliable inspection basis for strict control of cefathiamidine quality. [ABSTRACT FROM AUTHOR]

Background: The current investigation entails the characterization of seven degradation products (DPs) formed in different stress conditions of gilteritinib employing liquid chromatography-tandem mass spectrometry (LC-MS/MS). Methodology: This study developed a stability-indicating reversed-phase high-performance liquid chromatographic (HPLC) method for precisely determining gilteritinib in the presence of its process-related impurities in bulk drug and formulation samples. To explore the stability profile of gilteritinib, it was exposed to forced degradation experiments conducted under various conditions, including acidic, basic, oxidative, photolytic, and thermal stress. These experiments revealed the degradation of gilteritinib under basic, acidic, and photolytic conditions, forming seven distinct DPs. Result: The chromatographic resolution of gilteritinib and its impurities along with DPs was effectively achieved using a Waters Symmetry C18 (250 mm × 4.6 mm, 5 μm) column using equal volumes of solvent A and B (pH 4.5 phosphate buffer and acetonitrile in 25:75 (v/v) as solvent A, acetonitrile and methanol in 75: 25 (v/v) as solvent B) pumped isocratically at 0.7 mL/min and 230 nm wavelength. The method produces an accurate fit calibration curve in 25-175 μg/mL for gilteritinib and LOQ (0.025 μg/mL) – 0.175 μg/mL for its impurities with acceptable precision, accuracy, and recovery. Conclusion: The efficacy of this method was validated through LC-MS/MS, which allowed for the verification of the chemical structures of newly generated degradation products of gilteritinib. Hence, this method is appropriate for the resolution and evaluation of process-related impurities of gilteritinib and can also be applied for evaluating stress degradation products.

Investigating products under stress conditions provides valuable information for assessing stability, biosimilarity, and degradation behaviors during monoclonal antibody (mAb) development. Proper sample preparation is crucial for accurately evaluating the biosimilarity and effects of stress conditions in comparability assessment, where these studies guide biosimilar mAb development steps. Enzymatic and chemical treatments applied during sample preparation of mAbs generally require treatment of samples in temperatures higher than the storage temperatures of antibodies.In this study, samples of a TNF-α inhibitor IgG1 biosimilar (BIO) and its originator (OR) were treated for 7 days at commonly used temperatures during sample preparation. Alterations in the intact IgG, size variants, charge variants, binding kinetics, and post-translational modifications (PTMs) were investigated with CE-SDS, SE-UPLC, icIEF, SPR, and LC-MS/MS, respectively. Samples treated at 50 °C exhibited significant degradation, while minor differences were observed in samples treated at 37 °C. Monomer and intact IgG levels were decreased to levels below 97 % and 94 %, respectively, after 7 days of thermal treatment at 50 °C for both BIO and OR samples. Similar rates of degradation were observed between the treated biosimilar and originator samples. The percent monomer degradation rate between the biosimilar and the originators was similar at 50 °C (p = 0.32). Thermal treatment increased acidic variant levels in the products of the BIO (23.10 %) and OR (23.16 %). During post-translational modification monitoring, an increase in pyroglutamic acid formation and a decrease in C-terminal lysine were observed after thermal treatments. Acidic variant alterations were associated with asparagine deamidation and N-terminal pyroglutamic acid formation. Post-translational modifications were mainly located at the Fc domain, with methionine oxidation and asparagine deamidation as the main modifications occurring at the Fab domain.In conclusion, these results revealed that prolonged thermal treatment under elevated temperatures induces molecular alterations, thereby facilitating the degradation of IgG1. In addition, our findings indicate that both BIO and OR lots exhibit similar degradation profiles when subjected to thermal treatments.

Au-based micro-electro-mechanical-system (Au-MEMS) capacitance accelerometers show high sensitivity by suppressing the mechanical noise because of the high mass density of gold (ρ = 19.3 g/cm3). On the other hand, their long-term reliability suffers from drift phenomena induced by the impurities incorporated in the key component during their fabrication process, such as the gold electroplating step. Herein, impurities in electroplated Au-based components for MEMS capacitive accelerometers are evaluated by thermal desorption spectrometry (TDS) measurements. The TDS measurement reveals that dominant desorption gases from the Au-based component are molecular hydrogen (H2) and water (H2O). These desorption gases are derived from impurities in the electroplated Au-based component, and the amount of these gases is significantly suppressed by a thermal treatment step. In conclusion, this study demonstrates that the electroplated Au-based component contains impurities originated from the fabrication process, and these impurities could be removed by a thermal treatment step.

The development of renewable and low‐carbon gases for injection into the gas grid obtained by different processes such as anaerobic digestion, pyrogasification, hydrothermal gasification, and methanation, followed by upgrading steps, increases the demand for analysis and characterization in order to fully manage their integration into the gas value chain. If the analysis of the main compounds (methane, carbon dioxide, hydrogen, and carbon monoxide) is well described, the analysis of impurities in renewable gases remains more challenging due to their various natures and quantities. After a brief description of renewable and low‐carbon methane production processes, the review focuses on the methods used for the analysis of the different compounds in renewable gases, from the main ones to impurities at ppbv levels. Gas chromatography (GC), coupled with different detectors, is the preferred technique, enabling the analysis and quantification of siloxanes, terpenes, oxygenates, and sulfur compounds. Recently, comprehensive two‐dimensional GC has been applied to renewable gases, increasing the number of compounds detected. Non‐chromatographic techniques are also reviewed. As sampling is of major importance in the search for reliable analyses, a whole section is devoted to this aspect. Among the available methods, pre‐concentration on adsorbent tubes emerges as the most relevant solution. [ABSTRACT FROM AUTHOR]

Given that impurities may affect the quality and safety of drug products, impurity identification and profiling is an integral part of drug quality control and is particularly important for newly developed medications such as solriamfetol, which is used to treat excessive daytime sleepiness. Although the high-performance liquid chromatography analysis of commercial solriamfetol has revealed the presence of several impurities, their synthesis, structure elucidation, and chromatographic determination have not been reported yet. To bridge this gap, we herein identified, synthesized, and isolated eight process-related solriamfetol impurities, characterized them using spectroscopic and chromatographic techniques, and proposed plausible mechanisms of their formation. Moreover, we developed and validated a prompt impurity analysis method based on ultrahigh-performance liquid chromatography with UV detection, revealing that its selectivity, linearity, accuracy, precision, and quantitation limit meet the acceptance criteria of method validation stipulated by the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use. Thus, the developed method was concluded to be suitable for the routine analysis of solriamfetol substances.

A series of matrix reference materials for 21 inorganic trace impurities in 2 mg/g cadmium telluride (CdTe) solution with five impurity concentration levels (0, 1, 2, 4, 8 ng/g) were developed. High purity (>99.999%) CdTe was used as raw materials and dissolved using HCl-HNO3 mixed acid, and then was doped with multi-elements solutions to prepare the candidate reference materials (RMs). Matrix-matched ICP-MS with internal standard calibration was established for certification, homogeneity test and stability test. Mass spectrum interferences of 106Cd1H on 107Ag and 114In1H on 115In could be effectively removed by optimizing argon gas flow parameters coupled with mathematical correction. The matrix suppressed effect was effectively corrected about 20%-60% by using matrix-matched method. The precision of consecutive analysis expressed as RSD (n=22) was reduced to approximately 1% by using internal standard calibration. The linearly correlation coefficient factors (R) of standard curves were greater than 0.999 for all elements. The limits of detection (LODs) ranged from 0.001 ng/g to 0.35 ng/g, and the spike recoveries ranged from 89.2% to 106.5%. The established method was further validated by using CRM EB507. The dissolution of packaging containers was investigated and the results showed that the impurity dissolution from HDPE (high density polyethylene) bottle was lower than that from PP (polypropylene) plastic bottle. Except for Ca and Se, the dissolution of elements of concern in 4 months was less than 0.2 ng/g, which met the requirement. All elements were tested by the established method, and the results showed that the homogeneity, long-term and short-term stability of RMs were satisfactory and the validity period was 12 months. The mass fractions of 21 elements were certified by using a collaborative characterization program with eight sophisticated participating laboratories and using HR-ICP-MS and Q-ICP-MS methods. The arithmetic mean values were taken as the certified values, and the uncertainty was systematically and comprehensively evaluated. The measured results ranged from 3.5 ng/g to 4.5 ng/g, and the RSD ranged from 1.2% to 8.5% from 8 labs. The average value was about 4.0 ng/g, which was consistent with the target values and the relative expanded uncertainty was about 7%. This series of matrix RMs fills the blank of relevant RMs at home and abroad, and it plays an important role in verifying the reliability of measurement methods and ensuring the consistency and traceability of measurement results.

Given that impurities may affect the quality and safety of drug products, impurity identification and profiling is an integral part of drug quality control and is particularly important for newly developed medications such as solriamfetol, which is used to treat excessive daytime sleepiness. Although the high-performance liquid chromatography analysis of commercial solriamfetol has revealed the presence of several impurities, their synthesis, structure elucidation, and chromatographic determination have not been reported yet. To bridge this gap, we herein identified, synthesized, and isolated eight process-related solriamfetol impurities, characterized them using spectroscopic and chromatographic techniques, and proposed plausible mechanisms of their formation. Moreover, we developed and validated a prompt impurity analysis method based on ultrahigh-performance liquid chromatography with UV detection, revealing that its selectivity, linearity, accuracy, precision, and quantitation limit meet the acceptance criteria of method validation stipulated by the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use. Thus, the developed method was concluded to be suitable for the routine analysis of solriamfetol substances. [Display omitted] • Synthetic routes for eight process-related solriamfetol impurities are reported. • Plausible mechanisms for the formation of all impurities are suggested. • A chromatographic impurity analysis method is developed and validated. [ABSTRACT FROM AUTHOR]

Three 1.3 GHz nine-cell large-grain superconducting niobium cavities were investigated with medium-temperature baking, using buffered chemical polishing to remove the impurity profiles from previous heat treatments. The average intrinsic quality factor in 2 K vertical tests of the cavities was 2.7 × 1010 at 16 MV m−1 with maximum accelerating gradients of 20–22 MV m−1. These promising values confirmed the effectiveness of an improved medium-temperature baking recipe for niobium cavities, beneficial for superconducting radiofrequency applications. Furthermore, resistance analysis demonstrated that medium-temperature baking reduced both the Bardeen–Cooper–Schrieffer (BCS) resistance and the residual resistance of the cavities. Impurity analysis on niobium samples provided some proof that the reduction in BCS resistance was due to the shortened electron mean free path while the reduction in residual resistance was probably associated with mitigation of the increase in interstitial impurity atoms. [ABSTRACT FROM AUTHOR]

A series of matrix reference materials for 21 inorganic trace impurities in 2 mg/g cadmium telluride (CdTe) solution with five impurity concentration levels (0, 1, 2, 4, 8 ng/g) were developed. High purity (>99.999%) CdTe was used as raw materials and dissolved using HCl-HNO3 mixed acid, and then was doped with multi-elements solutions to prepare the candidate reference materials (RMs). Matrix-matched ICP-MS with internal standard calibration was established for certification, homogeneity test and stability test. Mass spectrum interferences of 106Cd¹H on 107Ag and 114In¹H on 115In could be effectively removed by optimizing argon gas flow parameters coupled with mathematical correction. The matrix suppressed effect was effectively corrected about 20%-60% by using matrix-matched method. The precision of consecutive analysis expressed as RSD (n=22) was reduced to approximately 1% by using internal standard calibration. The linearly correlation coefficient factors (R) of standard curves were greater than 0.999 for all elements. The limits of detection (LODs) ranged from 0.001 ng/g to 0.35 ng/g, and the spike recoveries ranged from 89.2% to 106.5%. The established method was further validated by using CRM EB507. The dissolution of packaging containers was investigated and the results showed that the impurity dissolution from HDPE (high density polyethylene) bottle was lower than that from PP (polypropylene) plastic bottle. Except for Ca and Se, the dissolution of elements of concern in 4 months was less than 0.2 ng/g, which met the requirement. All elements were tested by the established method, and the results showed that the homogeneity, long-term and short-term stability of RMs were satisfactory and the validity period was 12 months. The mass fractions of 21 elements were certified by using a collaborative characterization program with eight sophisticated participating laboratories and using HR-ICP-MS and Q-ICP-MS methods. The arithmetic mean values were taken as the certified values, and the uncertainty was systematically and comprehensively evaluated. The measured results ranged from 3.5 ng/g to 4.5 ng/g, and the RSD ranged from 1.2% to 8.5% from 8 labs. The average value was about 4.0 ng/g, which was consistent with the target values and the relative expanded uncertainty was about 7%. This series of matrix RMs fills the blank of relevant RMs at home and abroad, and it plays an important role in verifying the reliability of measurement methods and ensuring the consistency and traceability of measurement results. [ABSTRACT FROM AUTHOR]

We review photoluminescence processes due to donor and acceptor impurities with concentrations ranging from 1 × 1010 to 1 × 1020 cmâˆ'3 in both uncompensated and compensated Si at 4.2 K for application to the impurity characterization. Systematic evolution and extinction were observed in the impurity bound exciton and impurity cluster bound exciton emission, donor-acceptor pair emission with and without discrete sharp lines, donor-bandâ€"toâ€"acceptor-band emission, and the emission involving the intrinsic degenerate band. These variations occur as results of the transition from isolated impurity levels to interacting impurity levels due to impurity pairing or clustering in the concentration range around 1 × 1016 cmâˆ'3, the formation of the impurity bands in the range mid 1017 cmâˆ'3, and their unification with the intrinsic bands at critical Mott concentration of 3 × 1018 cmâˆ'3. Multiple radiative processes coexist in the transition regions and their intensities are determined by the impurity concentrations and the radiative probability of respective processes. [ABSTRACT FROM AUTHOR]

Etimicin is a typical aminoglycoside antibiotic (AG). High performance liquid chromatography-evaporation light scattering detector (HPLC-ELSD) method is a commonly used method for determining impurities in Etimicin. However, due to the poor reproducibility, low sensitivity and narrow linear range of the ELSD, high-throughput quantitative analysis of impurities in Etimicin currently poses a challenge. In this study, a sensitive method using hydrophilic interaction liquid chromatography coupled with charged aerosol detector (HILIC-CAD) was developed for the analysis of the impurities in Etimicin. The liquid phase conditions for determination impurities in Etimicin were optimized using Box Behnken design (BBD) and response surface methodology (RSM), resulting in satisfactory separation and optimal CAD output signal. We also studied the influence of CAD parameters on the signal-to-noise ratio and linearity of Etimicin and its impurities. This method has also been proven to be effective in separating impurities from two other typical AGs, Isepamicin and Amikacin. In the method validation, the coefficient of determination (R2) of Etimicin, Isepamicin and Amikacin and their impurities were all greater than 0.999, within the range of 0.5–50 μg/mL. The average recoveries of the impurities of three typical AGs were 99.03 %-101.22 %, RSDs all were less than 2.5 % for intra-day and inter-day precision, with good precision and accuracy. The developed HILIC-CAD quantification method was sensitive, accurate and highly selective for quantitative analysis of impurities in the AGs without need ion-pairing reagents, which is ensure the public medication safety. The method is first reported application of HILIC-CAD method for quantitative analysis of the impurities in AGs. • A HILIC system for separation of impurities in Etimicin was developed. • Establish a CAD method for determination impurities without UV absorption. • Liquid phase was optimized for good separation and output signal of CAD by RSM. • The CAD parameters were optimized for good S/N and linearity. [ABSTRACT FROM AUTHOR]

Impurities in nine dietary supplements containing l-tryptophan were evaluated using an HPLC methodology. In five tested products, the total impurities were higher than the thresholds described in the Food Chemical Codex or implemented in the EU for pharmaceutical grade l-tryptophan. In addition, liquid chromatography–mass spectrometry was used to specifically test for the presence of 1,1′-ethylidenebis-l-tryptophan (EBT). None of the tested products contained detectable amounts of EBT. High amounts of unidentified impurities in some dietary supplements point to potential health risks. [ABSTRACT FROM AUTHOR]

Simultaneous separation of the enantiomer and impurities is a huge challenge for the quality control of the chiral drug. In this work, mixed‐mode chiral ligand exchange stationary phases (CSPs) modified by octyl and sulfhydryl ligands were prepared by vapor deposition and click chemistry methods. Qualitative and quantitative determination of the prepared CSPs were achieved by Fourier transform infrared spectroscopy, solid‐state 13C CP/MAS NMR, and elemental analysis. The chiral resolution of CSPs was investigated through a comprehensively chromatographic evaluation of various racemates. Besides, the thermodynamic experiment was carried out to elucidate the contribution of hydrophobic ligand to the improvement of chiral recognition and selectivity. Atenolol and its degradation products were analyzed on the synthesized CSPs and compared with the commercial chiral column. A good separation of atenolol enantiomers from its acid and alkaline degradation impurities was simultaneously achieved on the C8/L‐Hypro CSP. This new CSP is expected to have more applications in the quality control of other chiral drugs. [ABSTRACT FROM AUTHOR]

A certified reference material (CRM) of sulfur dioxide (SO2) gas, with a certified value of purity, was developed for the preparation of primary reference gas mixtures of SO2 in nitrogen (N2) gas. Impurity analyses by "subtraction method" were performed using a gas chromatograph (GC) with a thermal conductivity detector (TCD), a GC with a flame ionization detector (FID), and a Fourier transform infrared spectrometer (FT-IR), all calibrated with gas mixtures traceable to the Internal System of Units (SI). First, qualitative analysis using the FT-IR was performed on two samples of liquefied SO2 of different quality grades, contained in gas cylinders. Using the FT-IR and the GC-TCD, carbon dioxide (CO2) was detected in the lower- and higher-grade cylinders at approximately 0.5 cmol/mol and 5 µmol/mol, respectively. The FT-IR did not detect any sulfur compound peaks, other than SO2, in the higher-grade sample. Other atmospheric constituents such as N2, oxygen (O2), water (H2O), argon (Ar), and methane (CH4) were also tested for in this sample. The detection limit of H2O in the FT-IR was 49 µmol/mol, while those of N2, O2, Ar, by the GC-TCD were a few µmol/mol, and CH4, using the GC-FID, were better than 1 µmol/mol. The high detection limit of H2O was due to large baseline fluctuations when measuring the FT-IR spectrum of the SO2 gas. Responses corresponding to these analytes were not detected or were detected below the detection limits. For an estimation of purity by the subtraction method, each reported mol fraction was regarded as half the value of each detection limit, except for the CO2. The purity and its expanded uncertainty [k = 2] of the high-purity SO2 gas by the subtraction method were 99.9964% and 0.0028%, respectively. [ABSTRACT FROM AUTHOR]

Copyright of Cotton Textile Technology is the property of Cotton Textile Technology Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Bopu powder® and Sangrovit® were developed from Macleayacordata and are widely used in agriculture and animal husbandry, but their impurities have been rarely reported in the literature. Impurity analysis is of great importance to the quality and safety of veterinary drugs. In this study, high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS) combined with a screening method was used to screen and characterize the impurities in Bopu powder® and Sangrovit®. A total of 58 impurities were screened from Bopu powder® and Sangrovit® using the screening strategies, of which 39 were identified by their accurate m/z value, characteristic MS/MS data, and fragmentation pathways of references. This established method was used for impurity analysis for the first time and proved to be a useful and rapid tool to screen and identify the impurities of Bopu powder® and Sangrovit®, especially for those at trace levels in a complex sample. In addition, this study marks the first comprehensive research into impurities in these two products and has great significance for the systematic detection of impurities in other plant-derived drugs.

Copyright of Cotton Textile Technology is the property of Cotton Textile Technology Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Highlights • Using HPTLC plates for solvent-free nanomole-scaled on-surface synthesis. • Miniaturized synthesis, workup and analysis performed on one HPTLC plate. • Tool for rapid impurity analysis of an anti-cancer drug. • On-surface synthesis enabled impurity signal highlighting in HPTLC-HRMS. Abstract On-surface reactions were introduced as a new strategy for rapid structure elucidation. This strategy is illustrated by the miniaturized synthesis-guided identification of two new degradation products (impurities) occurring in a pharmaceutical formulation of the anti-cancer drug ifosfamide, especially in the presence of urea. Synthesis on the silica gel surface bypassed the need for solvents, as the large nm-porous surface favoured a fast conversion of the reaction partners. For the on-surface synthesis of the impurities, the respective reagents were accurately and automatedly applied in the nanomole scale on a high-performance thin-layer chromatography (HPTLC) silica gel plate. After a fast reaction, the workup of the reaction mixture was performed by development of the HPTLC plate followed by online high-resolution mass spectrometry. As proof of concept and for benchmarking, a reaction mixture obtained from conventional preparative synthesis in a round-bottom flask was analysed in parallel as well as different formulations. The use of adsorbents as inert layer turned out to be highly efficient for a rapid generation and confirmation of impurities, as the synthesis on the HPTLC layer revealed them within 10 min. Image evaluation was simply performed by videodensitometry. The advantageous combination of all steps on one HPTLC plate and its resulting efficiency made surface synthesis on chromatographic phases an optimal tool for signal highlighting in mass spectrometry, and thus for the assignment of impurities in drugs. The chemistry process scale was miniaturized down to the μg-level per synthesis (in total 30-60 μg chemicals/reaction), setting a new state-of-the-art standard. All material savings clearly contribute to green chemistry, and this strategy substantially reduces the consumption of chemicals and greatly enhances the analytical efficiency, when adapted by scientists for the quality control of any other chemical product. The combination of synthesis, workup and detection in a miniaturized process, contributes to optimized workflows in a lean laboratory. [ABSTRACT FROM AUTHOR]

In the prescreening stage of full analysis for pesticide，direct analysis methods (GC-MS，LC-MS， LC-NMR etc. ) and synthetic verification method were often combined to obtain better qualitative results. Three main impurities in pyraclostrobin technical concentrate (TC) were isolated and analyzed using liquid chromatography-mass spectrometry (UPLC-MS) and higher energy collision induced disassociation (HCD). The liquid chromatograms were determined on UPLC equipped with C18 reversed phase column. The corresponding mass data was collected in positive ion mode of ESI on a high-resolution accurate-mass Orbitrap. The HCD MS/MS spectra of pyroclostrobin and impurity B and C showed that both the even-electron fragment cations and the odd-electron cations were observed. The structures of three impurities were estimated from the MS spectra, MS/MS spectra and the synthetic route. The structure of impurity A was estimated by comparing its MS/MS spectra with pyraclostrobin, it may be generated from the nitro-derivative in the hydrogenation step. In the MS/MS data of impurity B, m/z 63. 000 1 was observed and attributed to fragment of ClCH2CH2+ , thus impurity B may be generated by the reaction of hydroxylamine intermediate with the solvent dichloroethane. Impurity C may be due to the excess amount of Br2 in the bromination process, it was difficult to determine position of extra Br atom. From the perspective of systhesis process there were two possibilities: 1) Br atom was attached to the benzyl group; 2) Br atom was attached to thepyrazole ring. For impurity C，m/z 194. 080 8 was observed instead of m/z 271. 991 7 , which indicated that the Br atom was more likely to be attached to the pyrazole ring part. In order to confirm the above results，standards of impurity A，B and C were synthesized and analyzed using LC-MS. The results showed that the retention time，mass data of the standards were in accordance with the impurities in TC. It could be concluded that the main impurities of pyraclostrobin came from the side-reaction of the intermediates，and all of them showed good response in the ESI mass spectra. This study would benefit not only the preparation and quality control ，but also the registration of pyraclostrobin. [ABSTRACT FROM AUTHOR]

• Deposited impurities elements on divertor dome graphite tile of HL-2A primarily are Fe, Cr, Ni, Mn, Ca, Al, Cu, Si, and C. Among them, elements Fe, Cr, Ni, Mn, and al are deposited in proportion. • The ablation rate of the deposited layer is 348 nm/pulse at the laser fluence of 10 J /cm2 and the thickness of the deposited layer varies from 1.74 μm to 5.92 μm along the poloidal direction of HL-2A tokamak. • Depth distributions of each element are different along the poloidal direction, the absolute depth distribution of each element is also measured precisely. During tokamak discharges, the Plasma Wall Interaction (PWI) would lead to impurity deposition and fuel retention on the surface of the Plasma Facing Materials (PFMs). Laser-induced breakdown spectroscopy (LIBS) has emerged as a promising technique to facilitate in-situ, real-time, online characterization of the impurity deposition and fuel retention on the wall of tokamaks for PWI studies. The purpose of this investigation is to quantify the impurity deposition layer on the graphite tile removed from the dome region of the HL-2A tokamak lower divertor by using the ex-situ LIBS approach. The investigations indicate that the primarily deposited impurity elements are Fe, Cr, Ni, Mn, Ca, Al, Cu, Si, C, which may originate from the stainless steel first wall, divertor, limiter or the siliconized wall conditioning due to the PWI process in HL-2A tokamak. This has been further supported by observing a significantly positive correlation between the Cr, Ni, Mn, Al and Fe elements by spectral cumulative intensity linear regression analysis. The 3D morphology of the laser-ablated craters is reconstructed using a confocal microscope, revealing the laser ablation rates for the deposition layer and the substrate graphite tile to be 348 nm/pulse and 220 nm/pulse, respectively, under the laser fluence of 10 J/cm2. Then the thickness of the deposition layer is determined by using the correlation coefficient method. Along the poloidal direction of HL-2A tokamak, the deposited impurity shows an inhomogeneous pattern, with the thickness of the deposition layer varying from 1.74 μm to 5.92 μm. Finally, the absolute depth distribution of each element is also quantitatively measured. [ABSTRACT FROM AUTHOR]

The illegal drug 3,4-methylenedioxymethylamphetamine, also known as MDMA, ecstasy or ‘E’, synthesised as the hydrochloride and then made into tablets, has organic impurities arising from manufacture that can be used to profile seized material. Knowing if two samples come from the same batch gives strategic information about the drug manufacturing trade. We report similarity measures (Pearson correlation coefficient, reported as the modified Pearson distance, and its Fisher transform) between impurity content of pairs of samples manufactured using four common reductive amination routes. Powder and tablets are compared using the n th root of GC–MS peak normalised areas of 8 or 31 impurities, ( n = 2, 3, 4, 5, 10). Overall using 31 compounds with 4th root pre-treatment gave the best discrimination. PtO 2 /H 2 , and Al/Hg reductions were completely discriminated among batches while NaBH 4 and NaBH 3 CN routes gave around 4% false assignments. Synthesis parameters were systematically altered to determine what parameters have significant effects on the overall purity of the product and on the impurity profiles. The amount ratio of methylamine and MDP2P, and the temperature control of the reaction mixture were both significant. Comparison of modified Pearson's distances ( r scaled to ∈[0–100]), the Fisher transform of r , and ROC curves are simple ways of providing initial evidence whether seized drugs originate from the same batch. [ABSTRACT FROM AUTHOR]

Electrical power sources used in outer planet missions are a key enabling technology for data acquisition and communications. State–of-the-art power sources generate electricity from alpha decay of 238 Pu via thermoelectric conversion. However, production of 238 Pu requires specialist facilities including a nuclear reactor, a source of 237 Np for target irradiation and hotcells to chemically separate neptunium and plutonium within the irradiated targets. These specialist facilities are expensive to build and operate, so naturally, a more economical alternative is attractive to the space industry. Within Europe 241 Am is considered a promising alternative heat source for radioisotope thermoelectric generators (RTGs) and radioisotope heating units (RHUs) since, as a daughter product of 241 Pu decay, 241 Am exists in 1000 kgs quantities within the UK civil plutonium stockpile. A chemical separation process is required to extract the 241 Am in a pure form and this paper describes the AMPPEX process (Americium and Plutonium Purification by Extraction), successfully developed over the past five years to isolate 241 Am in high yield (> 99%) and to a high purity (> 99%). The process starts by dissolving plutonium dioxide in nitric acid with the aid of a silver(II) catalyst, which is generated electrochemically. The solution is then conditioned and fed to a PUREX type solvent extraction process, where the plutonium is separated from the americium and silver. The plutonium is converted back to plutonium dioxide and the americium is fed forward to a second solvent extraction step. Here the americium is selectively extracted leaving the silver in the aqueous phase. The americium is stripped from the solvent and recovered from solution as americium oxalate, which is calcined to give americium dioxide as the final product. This paper describes the development of the AMPPEX process over a series of six solvent extraction separation trials using centrifugal contactors. The technical underpinning reported here has allowed the design of a facility capable of producing 25-50 g of americium per day. [ABSTRACT FROM AUTHOR]

Samples of materials involved in the conversion of uranium into nuclear-grade products are collected to support the verification of States' declarations and to look for indications of possible undeclared materials and activities. Samples are analysed by several laboratories to determine concentrations of about sixty impurities; the data consistency is addressed through the unified reporting requirements, the use of common reference materials, and via inter-laboratory comparisons. The impurity analysis results, along with other essential parameters, are interpreted to judge sample conformity to the relevant specifications, to evaluate the facility design information, to assess material provenance and intended use. [ABSTRACT FROM AUTHOR]

A novel simple, fast and efficient supercritical fluid chromatography (SFC) method was developed and compared with RPLC method for the separation and determination of impurities in rifampicin. The separation was performed using a packed diol column and a mobile phase B (modifier) consisting of methanol with 0.1% ammonium formate (w/v) and 2% water (v/v). Overall satisfactory resolutions and peak shapes for rifampicin quinone (RQ), rifampicin (RF), rifamycin SV (RSV), rifampicin N-oxide (RNO) and 3-formylrifamycinSV (3-FR) were obtained by optimization of the chromatography system. With gradient elution of mobile phase, all of the impurities and the active were separated within 4 min. Taking full advantage of features of SFC (such as particular selectivity, non-sloping baseline in gradient elution, and without injection solvent effects), the method was successfully used for determination of impurities in rifampicin, with more impurity peaks detected, better resolution achieved and much less analysis time needed compared with conventional reversed-phase liquid chromatography (RPLC) methods. [ABSTRACT FROM AUTHOR]

A new stability indicating reversed phase high performance liquid chromatography (RP-HPLC) method was developed and validated under current International Conference of Harmonisation (ICH) guidance for the determination of prednisolone acetate (PAC) and impurities in an ophthalmic suspension. The developed method is presented as an alternative to a modified version of the current RP-HPLC method described in the USP monograph for the assay of PAC in an ophthalmic suspension. Along with the assay of PAC, the new method is also capable of identifying and quantifying eight selected PAC impurities and degradation products in an ophthalmic suspension. Using an Agilent Poroshell 120 EC-C18 100 mm × 4.6 mm ( d p : 2.7 μm) column set to 60 °C with step gradient elution generated using mobile phase A: acetonitrile/water (10:90) (v/v) and mobile phase B: acetonitrile delivered at 1.2 mL min −1 , all peaks of interest are eluted in 33 min with resolution of 1.5 between the critical pairs. The developed method was validated for PAC and impurities to ICH recommendations for accuracy, linearity, precision (repeatability), limit of detection, limit of quantitation, robustness and specificity. [ABSTRACT FROM AUTHOR]

An intercomparison was organized, with six laboratories tasked to quantify sixty-nine impurities in two uranium materials. The main technique employed for analysis was inductively coupled plasma mass spectrometry in combination with matrix-matched external calibration. The results presented highlight the current state-of-the-practice; lessons learned include previously unaccounted polyatomic interferences, issues related to sample dissolution, blank correction and calibration, and the challenge of estimating measurement uncertainties. The exercise yielded consensus values for the two analysed materials, suitable for use as laboratory standards to partially fill a gap in the availability of uranium reference materials characterized for impurities. [ABSTRACT FROM AUTHOR]

Abstract: Based on secondary ion mass spectrometry (SIMS) measurements, we have compiled state-of-the-art data concerning dopant elements and natural impurities in the wide bandgap semiconductor materials diamond, SiC, ZnSe, GaN and AlN. Samples were prepared by ion implantation of different elements into these materials and post-implantation thermal annealing. SIMS depth profiling techniques were used to determine atomic depth profiles of implanted elements and subsequent changes produced by annealing. Range statistics and SIMS relative sensitivity factors were established for major dopant and impurity elements in these wide bandgap materials. Results of these studies are presented in tabular form along with representative depth profile figures. [Copyright &y& Elsevier]

Abstract: Combining the most powerful separation techniques, i.e. liquid chromatography (LC) or capillary electrophoresis (CE) with a information rich detection system – the mass spectrometer or the nuclear magnetic resonance (NMR) spectrometer – has been pursued for more than three decades. This compilation shall provide an overview of the advantages and limitations of the LC–NMR hyphenation in the light of its most valued application–the unequivocal analyte identification. Especially the post LC trapping of analytes with an in-line solid phase extraction (SPE) device prior to transferring the analyte of interest to the NMR spectrometer (LC–SPE–NMR) proved to be a robust installation allowing a significant cut-down of the amount of analyte needed for the generation of high quality heteronuclear NMR shift correlation data. Different available technical realizations will be discussed and typical application examples from natural product research and from industrial settings will be given. [Copyright &y& Elsevier]

Abstract: Monofunctional maleimide polyethylene glycol (mono-mal-PEG) with average molecular weight up to 40kDa can be used as a raw material for the PEGylation of therapeutic proteins. A possible impurity in this raw material which needs to be controlled is the bisfunctional maleimide-PEG, which has a similar average molecular weight to mono-mal-PEG. Chromatographic separation and detection of low level bis-mal-PEG in mono-mal-PEG presents a major challenge because of the polydispersity of the analytes and the minor difference between the desired mono-mal-PEG and the bis-mal-PEG impurity. In this study, linear mal-PEGs were first derivatized with a specially designed cys-peptide containing a UV chromophore and multiple ionizable sites. Separations were then carried out by reversed-phase HPLC with UV detection at 360nm. Mono-mal-PEG and bis-mal-PEG were well resolved using a Gemini C18 column with an aqueous-acetonitrile mobile phase. Retention times increased as PEG molecular weight increased from 10kDa to 40kDa, while selectivities decreased as PEG molecular weight increased. Results from systematically designed studies for optimization of critical parameters including gradient slope, column temperature, and acidic modifier in the mobile phase led to the selection of the final separation conditions. The developed method conditions were specific, accurate, and sensitive for detecting bis-mal-PEG as an impurity in mono-mal-PEG with limit of quantitation of 0.2% and may be used to assess the quality of mono-mal-PEG as a raw material for protein PEGylation. [Copyright &y& Elsevier]

In this paper, impurity parameters m and k have been calculated for a range of impurities I as detected in the eutectics Co-C and Pt-C, by means of the software package Thermo-Calc within the ternary phase spaces Co-C- I and Pt-C- I. The choice of the impurities is based upon a selection out of the results of impurity analyses performed for a representative set of samples for each of the eutectics in study. The analyses in question are glow discharge mass spectrometry (GDMS) or inductively coupled plasma mass spectrometry (ICP-mass). Tables and plots of the impurity parameters against the atomic number Z of the impurities will be presented, as well as plots demonstrating the validity of van't Hoff's law, the cornerstone to this study, for both eutectics. For the eutectics in question, the uncertainty u( T − T ) in the correction T − T will be derived, where T and T refer to the transition temperature of the pure system and to the liquidus temperature in the limit of zero growth rate of the solid phase during solidification of the actual system, respectively. Uncertainty estimates based upon the current scheme SIE-OME, combining the sum of individual estimates (SIE) and the overall maximum estimate (OME) are compared with two alternative schemes proposed in this paper, designated as IE-IRE, combining individual estimates (IE) and individual random estimates (IRE), and the hybrid scheme SIE-IE-IRE, combining SIE, IE, and IRE. [ABSTRACT FROM AUTHOR]

As a continuation to earlier work on the silver-point realization, already reported at TEMPMEKO 2007, a new silver-point cell has been fabricated using 6N-nominal grade material that was analyzed by means of glow discharge mass spectrometry (GDMS) by the manufacturer. This new cell is evaluated by a direct cell comparison with one of the existing cells, which was also already reported at TEMPMEKO 2007. One of those existing cells was drawn out from its crucible, and its ingot was analyzed by GDMS at four positions, namely, at around the center of the top, of the middle, of the bottom, and around the outer part of middle areas for the purpose of confirming whether or not there has been differences in the content of impurities before and after the cell fabrication, as well as differences in impurity homogeneity within the ingot. As results of the aforementioned measurements, it was found that the homogeneity of impurities in the silver ingot was on average within 50 %. It was also found that cell-to-cell temperature differences change along with the progressing solidification process. As a consequence, it was concluded that, for an accurate cell-to-cell comparison, the location in the freezing plateau, where the comparison is done, should be determined. Also obtained here is that the slope analysis was consistent with both the cell-to-cell comparison and the impurity analysis. [ABSTRACT FROM AUTHOR]

Several gentamicin bulk samples from different origins were investigated using an LC/MS method. LC equipped with ion trap MS with positive ionization was performed on a Capcell Pak C (AQ) column with the mobile phase containing 50 mM trifluoroacetic (TFA) and methanol. Impurities present in batches of gentamicin bulk samples were elucidated and compared according to their fragmentation behavior. In total seventeen impurities present in samples, five impurities were not elucidated and two compounds were identified preliminarily. It was observed that the impurity profiles were different in samples from different origins which indicate necessity in the quality control of gentamicin. [ABSTRACT FROM AUTHOR]

Two unknown impurities were detected in verapamil hydrochloride bulk drug using isocratic reversed-phase high performance liquid chromatography (HPLC). These impurities were isolated by preparative HPLC. Spectral data for the isolated impurities were collected. Based on the spectral data derived from two-dimensional nuclear magnetic resonance (2D-NMR) spectroscopy and mass spectrometry (MS), impurity-1 and impurity-2 were characterized as 2-(3,4-dimethoxyphenyl)-3-methylbut-2-enenitrile and 2-(3,4-dimethoxyphenyl)-2-isopropyl-3-methylbutanenitrile, respectively. [ABSTRACT FROM AUTHOR]

Abstract: While supercritical fluid chromatography (SFC) has received great popularity in chiral separation and purification, it has rarely been used for trace level pharmaceutical impurity analysis, partially due to the limitation of instrument sensitivity. In this study, a packed column SFC method has been developed for the quantitative analysis of mometasone furoate and its trace level impurities. The UV detection was optimized to improve the sensitivity by 2–4 fold. In combination with an increased sample concentration, this SFC method is capable of trace level (0.05% of the active) analysis of the impurities. The SFC method used a silica column and a mobile phase consisting of CO2 and methanol. The new method provides an orthogonal selectivity complementary to the reversed phase HPLC (RP-HPLC) method. All of the impurities and the active were baseline separated within 12min on SFC, which is less than one third of the RP-HPLC method run time. The method was also partially validated for linearity, accuracy, precision (repeatability), and limit of quantitation. This study demonstrated that the SFC method, with improved sensitivity, can be a valuable tool to provide orthogonal selectivity for trace level impurity separation. With further validation, the method may be suitable for release testing and stability testing for mometasone furoate drug substance. [Copyright &y& Elsevier]

Continuing our study on aluminum, tin, and silver points, a study on the realization of the zinc point was conducted. Zinc-point cells were newly fabricated using 6N-nominal grade zinc samples, impurity elements of which were analyzed extensively based on glow-discharge mass spectrometry (GDMS). The present paper reports the temperature measurements done using the newly fabricated cells during the zinc freezing process, under which the zinc fixed point is defined, and the analysis of the freezing curve obtained. Comparisons of zinc-point temperatures realized by the newly fabricated cells (cell-to-cell comparisons) were also conducted. Zinc-point depression due to impurity elements was calculated based on the sum of individual estimates and the impurity element analysis. One of the cells evaluated was drawn out from its crucible and analyzed by GDMS at four points, namely, at around the center of the top, of the middle, of the bottom, and around the outer part of the middle area. The purpose of this cell disassembly is to see whether or not there has been some difference before and after cell fabrication, as well as difference in impurity element distribution within the ingot. From the aforementioned studies, some findings were obtained. First finding is that the homogeneity of the zinc ingot was within 30%, except for Pb, which was more concentrated in the center part. Second finding is that the cell-to-cell temperature difference changes along with the progressing solidification process. As a consequence, for an accurate cell-to-cell comparison, the locus in the freezing plateau where the comparison is done should be determined. Third finding is that the slope analysis estimates accurately the cell-to-cell comparison, and is consistent with the impurity analysis. This shows that the slope analysis gives extensive information about the effect of impurity to the zinc-point realization, especially after the cell fabrication. [ABSTRACT FROM AUTHOR]

Abstract: A chiral microemulsion electrokinetic chromatography method has been developed for the separation of the enantiomers of the phenethylamines ephedrine, N-methylephedrine, norephedrine, pseudoephedrine, adrenaline (epinephrine), 2-amino-1-phenylethanol, diethylnorephedrine, and 2-(dibutylamino)-1-phenyl-1-propanol, respectively. The separations were achieved using an oil-in-water microemulsion consisting of the oil-component ethyl acetate, the surfactant sodium dodecylsulfate, the cosurfactant 1-butanol, the organic modifier propan-2-ol and 20mM phosphate buffer pH 2.5 as aqueous phase. For enantioseparation sulfated β-cyclodextrin was added. The method was compared to an already described CZE method, which made use of heptakis(2,3-di-O-diacetyl-6-O-sulfo)-β-cyclodextrin (HDAS) as chiral selector. Additionally, the developed method was successfully applied to the related substances analysis of noradrenaline, adrenaline, dipivefrine, ephedrine and pseudoephedrine monographed in the European Pharmacopoeia 6. [ABSTRACT FROM AUTHOR]

The effects of acids on the removal of impurity from 2N grade silica have been studied using five leaching acids: 0.2 M-oxalic acid (pH 1.5 and 2.5), c-aqua regia, 2.5%—HCl/HF, and 1%—HNO3/HF. The presence of 39 impurities in the 2N grade silica and the reference material (RM, 5N grade silica) were investigated by neutron activation analysis (NAA), X-ray fluorescence (XRF), and inductively coupled plasma mass spectrometry (ICP-MS) methods. Major impurities of the 2N silica were Al, K, Fe, Na, Ti, Ca, Mg and P. The fractions of the eight major impurities were 99.2% and 90.9% of total impurity in the 2N and RM silica, respectively. Among the leaching acids, almost all of the major impurities were removed effectively by the 2.5% HCl/HF leaching acid. All the major impurities, except for phosphorous, as well as 21 minor and trace impurities could be determined by the NAA. [ABSTRACT FROM AUTHOR]

A new, sensitive LC–MS method for evaluation of the purity of Transkarbam 12 (T12), a novel and highly effective accelerant of transdermal penetration, has been developed and validated. T12 and its impurities (6-aminohexanoic acid, AH, ε-caprolactam, CA, and dodecyl 6-(6-aminohexanamido)hexanoate, DAH) were characterized by MS and MS–MS analysis. Separation was achieved on a 150 mm × 3 mm, 5-μm particle, phenyl–hexyl column. The mobile phase was a gradient prepared from water, formic acid, and acetonitrile. The method was validated within the concentration range 50–250 ng mL−1; correlation coefficients were >0.998. The accuracy of the method was from 98.6–105.0% for AH, 102.6–104.8% for CA, and 97.9–100.9% for DAH. Precision was in the range 3.19–4.42% for AH, 3.22–5.81% for CA, and 4.8–8.78% for DAH. The selectivity of the method and sample stability were also confirmed. The practical applicability of the method was proven by analysis of T12 bulk substance. [ABSTRACT FROM AUTHOR]

Abstract: Numerous combinations of one-, two-, and three-chiral-component microemulsions have been previously prepared in our group, using N-dodecoxycarbonylvaline (DDCV), 2-hexanol, and ethyl acetate, dibutyl tartrate, or diethyl tartrate. A few results of the various formulations investigated suggested the possible presence of minor impurities in one or more components of the microemulsion. In this study, the purity of the current lots of R- and S-surfactant were measured, as was the subsequent effect of minor impurities on the relevant chromatographic figures of merit (CFOMs) that describe a chiral separation, i.e., efficiency, enantioselectivity, retention, migration window (elution range), and resolution. Two related methods are proposed for correcting enantioselectivities measured in the presence of chiral impurities in the chiral microemulsion. [Copyright &y& Elsevier]

Abstract: A method for assessing the impurity 210At in cyclotron-produced 211At via isotope dilution alpha spectrometry is presented. The activity of 210At is quantified by measuring the activity of daughter nuclide 210Po. Counting sources are prepared by spontaneous deposition of Po on a silver disc. Activity of 210At (at the time of 210Po maximum activity) is found to be 83.5±9.0Bq, corresponding to an atom ratio (210At:211At at the time of distillation) of 0.010±0.007% (). The method produces high-quality alpha spectra, with baseline alpha-peak resolution and chemical yields of greater than 85%. [Copyright &y& Elsevier]

Abstract: A versatile procedure has been developed and validated for the determination of triphenylphosphine oxide (TPPO) at low levels in various active pharmaceutical ingredients (APIs). This procedure incorporates the use of the novel hollow-fiber liquid-phase microextraction (LPME) for the measurement of this potential process-related impurity in aqueous solutions of APIs. A small volume (40μL) of 1-octanol contained within a hollow polypropylene fiber is used for the extraction of TPPO from low pH aqueous API solutions. More than a 100-fold increase in the TPPO concentration is obtained without additional evaporation of the extract. Experimental parameters of the extraction procedure were investigated to optimize extraction efficiency and minimize sample matrix interference. Using HPLC/UV as the end analysis technique, the procedure was validated for TPPO in the concentration range of 3–16μg/L with an API present at 1500mg/L. The versatility of the method was demonstrated by applying the procedure to the analysis of APIs with different molecular structures. This simple LPME procedure is inexpensive and offers appropriate sensitivity for the intended use while providing several advantages over other analysis methods for pharmaceutical samples. [Copyright &y& Elsevier]