The Jiangmen Underground Neutrino Observatory (JUNO) is a 20 kton multi-purpose underground liquid scintillator detector designed to determine the neutrino mass hierarchy, and measure the neutrino ...oscillation parameters. The excellent energy resolution and the large fiducial volume anticipated for the JUNO detector offer exciting opportunities for addressing many important topics in neutrino and astro-particle physics. Linear alkylbenzene (LAB) will be used as the solvent for the liquid scintillation system in the central detector of JUNO. The light attenuation lengths of LAB should be comparable to the diameter of the JUNO detector, hence very good optical transparency is required. However, the presence of impurities in the LAB renders an intrinsic limit for the transparency. This work focuses on the study of the effects of organic impurities in the LAB, and their light absorption properties particularly in the wavelength region of 350–450 nm. We have prepared LAB samples and measured their light attenuation lengths. These samples were then analyzed by a gas chromatography–mass spectrometry (GC–MS), and the structure formulas of organic impurities were ascertained. These impurities’ light-absorption properties in the wavelength region of 350–450 nm were theoretically investigated with time-dependent density functional theory (TDDFT). The overall optical transparency of the LAB samples was studied, which would further help us in promoting the LAB preparation technique for the mass production thereof, thus improving the transparency of the high quality LAB samples in the near future.
Objective: The objective of the present study was to develop and validate a stability indicating RP-HPLC method for Lumefantrine (LF) and its organic impurities using a central composite design ...(CCD).
Methods: A specific, simple quality control friendly isocratic elution method using reverse phase HPLC was developed for quantification of Lumefantrine (LF) and its organic impurities at a wavelength of 265 nm. The chromatographic separation was achieved on the column of Thermo Hypersil ODS C18 (150x4.6 mm, 3µ) with a buffer containing 0.1percent formic acid and acetonitrile 10:90 v/v as a mobile phase with a flow rate of 1.6 ml/min at 35 °C with a run time of 10 min. Based on the preliminary trials, CCD was employed to check the effect of independent variables such as Acetonitrile ratio (A), Flow rate (B), and Column oven temperature (C). While resolution between Lumefantrine (LF) and Impurity-A (X1), Impurity-A and Impurity-B (X2), and Plate count of Lumefantrine (LF) (X3) were considered as dependent variables and statistical evaluation performed by using design expert software. The optimized conditions were validated as per ICH guidelines.
Results: The retention time of LF and its organic impurities were 1.9 min, 3.0, 4.5, and 6.4 min, respectively. Design space was established and desirability was found. LOD and LOQ for the Lumefantrine (LF) and its impurities were established with respect to test concentration. The plotted calibration curves were linear with a regression coefficient of R2>0.99, indicating that the linearity was within the limit. As a part of method validation, the parameters like Specificity with forced degradation, Linearity, Precision, Accuracy, Ruggedness, and Robustness were determined and the results were found to be within the allowable limits.
Conclusion: The method developed and validated was found to be suitable for routine analysis and to be used for the measurement of Lumefantrine and its impurities. Since there is no stability indicating the RP-HPLC method with design space was reported in the literature, there is a need to develop quantitative methods under different conditions to achieve improvement in specificity and selectivity.
Direct analysis in real time coupled with high-resolution mass spectrometry (DART-HRMS) followed by multivariate statistical analysis has been successfully applied to infer the sources of heroin ...samples seized in China. Heroin and organic impurities in samples were detected by DART-HRMS. Partial least squares- discriminant analysis (PLS-DA) and orthogonal PLS-DA (OPLS-DA) models were tested and compared using data for heroin seized from Southeast Asia and Southwest Asia. The OPLS-DA model was used to discover and identify potential organic impurities to distinguish heroin samples from different sources. Niacin, paracetamol, ephedrine, caffeine, hydrocotarnine, lidocaine, morphine, codeine, thebaine, boldine, reticuline, papaverine, codamine, papaveraldine, laudanosine, heroin, N-acetylnorlaudanosine, 3,6-dimethoxy-8-(2-(N-methylacetamido)ethyl)phenanthren-4-yl acetate, N,O3,O6-triacetylnormorphine, noscapine, reticuline diacetate, narceine and four unknowns were detected in our research. Unknown heroin samples were analysed by an established model to determine their sources. The proposed method shows that DART-HRMS combined with multivariate statistical analysis was a simple and effective method for judging the source of heroin. The low-pollution method established in this experiment was suitable for the high-throughput determination of heroin samples and was, simple, fast and accurate. This method, which was used to identify the sources of drugs, is a major innovation in forensic intelligence analysis.
•DART-HRMS was used to detect organic impurities in seized heroin to trace the source of the heroin.•Multivariate statistical analysis was used to establish a model to analyse unknown sources of heroin.•A total of 26 organic impurities were found in heroin samples by DART-HRMS.•The method established was suitable for the simple, fast and accurate high-throughput determination of heroin samples.
In this paper, a model is developed for calculating pH in the presence of organic impurities due to dissolution of paint and/or continuous injection of organic impurities in the sump. The model is ...implemented in the AnCheBi code for the analysis of chemical behaviors of the iodine in the containment when the pH changes during a severe accident. Validation of the model is performed with P10T2 and P11T1 experiments carried out by AECL in Canada under the BIP project. Importance analyses of the pH calculation model in the AnCheBi code are then performed with the aforementioned experimental data via Latin hypercube sampling on the reaction coefficients, sensitivity analyses of AnCheBi, and calculation of the correlation coefficients between the reaction coefficients and figure of merits (the pH and the concentrations of the various iodine species). From the importance analyses, we provide the sensitivity of the pH calculation model to the change of pH and the concentrations of the various iodine species and the reaction coefficients related with the dominant phenomena underlying the change of pH and the concentrations of the species.
A simple quality by design aided stability indicating method was developed for quantification of sonidegib (SONI) and its process related impurities using on ultra‐performance liquid chromatography ...in bulk drug substance. AutoChrom and Design‐Expert software were used to predict physicochemical properties, draw Ionization graphs, and generate analytical target profile. SONI was subjected to forced degradation conditions, such as oxidative, acid hydrolysis, base hydrolysis, hydrolytic, thermal, and photolytic hydrolysis. All degradation products and process contaminants were separated using an Acquity Ethylene Bridged Hybrid C18 column in gradient elution mode with a mobile phase containing 0.02 M ammonium acetate buffer and acetonitrile: methanol (80:20 v/v). The predicted physicochemical properties are accurate and they facilitated for selection of robust conditions in development of chromatographic method with minimal trials. The developed method can be used for quantification of drug and its process related impurities in bulk drugs.
The effect of the morphology and the crystallographic texture on the mechanical behavior of zinc electrodeposits is described. The mechanical behavior was assessed with a customized bending device ...and correlated to the main features of the deposit. The methodology proposed in this paper allows a better assessment of the effect of impurities (organics/inorganics) or additives on the quality of metal deposits, thereby assisting industry to optimize conditions and increase productivity. Bending tests carried out up to a bending angle of 50° revealed that the organic contaminants affect the mechanical properties of the zinc deposit differently. These properties were found to be strongly correlated to the electrodeposit's features. Highly porous deposits showed low ductility, which in turn caused the fracture of the sample at small bending angles, thus impeding effective stripping. The results obtained from the bending tests allowed a semi-quantitative prediction for the behavior of different zinc deposits during the stripping operation.
•Mechanical behavior of Zn deposits assessed with customized bending device.•Bending behavior (simulating stripping) correlated to deposit's features.•Organics affect morphology, texture and bending behavior of Zn deposits.•Highly porous deposits showed low ductility, impeding effective stripping.
Natural waters, water droplets in the air at coastal regions and wastewaters usually contain chloride ions (Cl
-
) in relatively high concentrations in the milimolar range. In the reactions of highly ...oxidizing radicals (e.g.,
•
OH,
•
NO
3
, or SO
4
•-
) in the nature or during wastewater treatment in advanced oxidation processes the chloride ions easily transform to chlorine containing radicals, such as Cl
•
, Cl
2
•-
, and ClO
•
. This transformation basically affects the degradation of organic molecules. In this review about 400 rate constants of the dichloride radical anion (Cl
2
•-
) with about 300 organic molecules is discussed together with the reaction mechanisms. The reactions with phenols, anilines, sulfur compounds (with sulfur atom in lower oxidation state), and molecules with conjugated electron systems are suggested to take place with electron transfer mechanism. The rate constant is high (10
7
–10
9
M
-1
s
-1
) when the reduction potential the one-electron oxidized species/molecule couple is well below that of the Cl
2
•-
/2Cl
-
couple.
Carbon contaminations on surface & sub-surface of silicon (Si) are characterized using Auger method. The surface carbon atomic % on Si of post treatment with H 3 PO 4 (for nitride etch), BOE (buffer ...HF for oxide etch) & SC1 (standard clean for organic removal) is 4.0%, 6.0% & 1.7% respectively, with significantly higher for sample of post BOE. BOE chemicals of fresh, mid-processing & end-processing baths were sampled for gas chromatography-mass spectrometry (GC-MS) analysis where significant amount of cyclopentasiloxane & benzene were detected using hexane extraction. Cyclopentatsiloxane & benzene level was reduced from 1.7 x 10 5 to 0.45 x 10 5 & 0.7 x 10 5 to 0.4 x 10 5 count per second (cps) respectively, from fresh to end-processing chemicals. This indicates that the organic impurities in the solution might have been adsorbed or incorporated into the Si layers during oxide etching process. Auger & GC-MS proved to be efficient in monitoring & controlling of organic impurities in semiconductor process.
A direct analysis in real time (DART) coupled with high-resolution mass spectrometry (HRMS) method was established to detect organic impurities in cocaine samples seized in China. This approach ...allowed discrimination between linked and unlinked seizures with quick sample preparation and high throughput. The responsivities of the mass spectra of 20 organic impurities found in 47 cocaine samples were explored as factors in multivariate analysis. Based on the data from 20 organic impurities in 47 linked/unlinked cocaine samples, 25 combinations of data pretreatment methods and distance/correlation measurements were compared to choose the combination with the best discriminating power for cocaine profiling. Data pre-treatment by calculating the logarithm (L) followed by Squared Euclidean distance (Squ Dij) was chosen as the best combination for the optimal discrimination of linked and unlinked samples. Hierarchical cluster analysis (HCA) was used to analyse another 46 cocaine samples, and 38 of the 46 cocaine samples were divided into 9 linked groups. Relevant information was provided for forensic science intelligence and case analysis.
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•Twenty organic impurities were found in 47 cocaine samples seized in China by DART-HRMS.•Twenty-five combinations of measurements were tested to find the combination with the best discriminating power, and hierarchical cluster analysis was used.•DART-HRMS was used to analyse actual cocaine samples, and the correlation information of cocaine samples was provided to the police.
INTRODUCTION. The determination of impurities is a key requirement for the quality assessment of medicines because impurities can significantly impact the quality and therapeutic effectiveness. ...Pharmacopoeias are the most important scientific and methodological guidelines for manufacturers developing medicinal product specifications and regulators assessing these specifications as part of registration dossiers. Therefore, it is essential to harmonise national and international approaches to impurities. AIM. This study aimed to analyse and summarise pharmacopoeial requirements for and methodological approaches to the control, evaluation, and identification of organic impurities in medicines. DISCUSSION. The authors compared requirements for the control of organic impurities in small-molecule medicines set forth in national and international pharmacopoeias and guidelines of the International Council for Harmonisation of Technical Requirements for Medicinal Products for Medical Use (ICH) and the Eurasian Economic Union (EAEU). This comparison highlighted the differences in current approaches that require further harmonisation of the existing regulatory documentation. Additionally, this study analysed the popularity, advantages, and disadvantages of different options for determining impurities in two-component combination products (i.e. identified and/or unidentified impurities in one or each of the active substances). The analysis demonstrated the need to control nitrosamines and genotoxic impurities and to use selective and highly sensitive chromatographic methods. CONCLUSIONS. When drafting pharmacopoeial monographs for medicinal products, experts should consider the general approach set forth in the EAEU pharmacopoeia and regulations and in the ICH Q3B guideline. This approach recommends that process-related impurities of active substances should not be controlled at the medicinal product level. Therefore, pharmacopoeial monographs for active substances should distinguish degradation products from process-related impurities. Impurities should be determined for each active substance to ensure the quality and safety of fixed combination medicinal products. Priorities for improving the methodological approach to the control of organic impurities include using reference standards for impurities and acknowledging the necessity of impurity quantification.
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