Differences In Impurities Research Articles

Quality Evaluation of Gentamicin Sulfate Reference Standards in Japanese Pharmacopoeia Using Hydrophilic Interaction Chromatography Combined With Tandem Mass Spectrometry.

Through the recent development of analytical technology, antibiotics quantification in the Japanese Pharmacopoeia (JP) has changed from traditional microbiological assays to physicochemical methods with high specificity and precision. However, for several multicomponent antibiotics without typical UV absorption, potency cannot be directly determined using instrumental methods such as high-performance liquid chromatography; therefore, traditional microbiological assays are still used. Gentamicin sulfate (GmS), which consists of three major components, C1, C1a, and C2, is such a typical antibiotic, and its antimicrobial potency continues to be assayed using microbiological methods in JP monographs. Introduction of a physicochemical assay for GmS is needed to help ensure its quality and quantity. This study aimed to develop quality control measures for GmS that could be complementary to quantitative assays and purity tests specified in the JP. For each gentamicin C component (C1, C2, and C1a), theoretical potencies were determined based on the quantitative relationship between purity and potency, as measured by quantitative 1H NMR and microbiological assays, respectively. Two lots of the JP reference standard (RS) were used as test samples, with the contents of each component and impurity (sisomicin and garamine) being determined using hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS). The ratios of theoretical potency for C1, C2, and C1a were 1.00, 1.21, and 1.80, respectively. The potencies of the GmS JP RSs, which were estimated based on the contents and theoretical potency of each C component, corresponded well with those determined through microbiological assays. Marked differences in impurities (%) between the two RS lots were highlighted by quantifying sisomicin and garamine. The developed analytical procedure enabled the characterization of two different JP RSs in terms of content ratio, potencies, and impurities. Novel analytical procedures useful for routine quality control of GmS were developed using HILIC-MS/MS.

Influence of silicon particle morphology on laser-induced plasma properties

In this work, Si particles of varying sizes and a bulk Si wafer are exposed to high-energy nanosecond-pulsed laser excitation. The subsequent laser-induced plasma is characterized using a suite of diagnostic techniques, including spatiotemporal species imaging via high-speed videography and high-resolution gated spectroscopy. The intensity and location of various species in the plasma (e.g., Si I and Si II) are tracked as a function of time over two time regimes, 2–10 μs and 20–80 μs, and show differences in impurities and peak intensities between the various particle sizes and compared to the Si wafer. Electron densities under these conditions decrease from ≈1.8 to 0.8 × 1017 cm−3 from 2 to 8 μs, while plasma excitation temperatures determined from the Boltzmann method range from 9200 to 8000 K over the same time window. The powdered Si samples have characteristically larger and more intense plasmas than the wafer sample. The laser-induced air-shock from energetic materials (LASEM) method was employed on these materials, in concert with their acoustic response, to establish their relative microsecond energy releases. While the powders have similar laser-induced shock velocities, they appear to have differences in their acoustic response which roughly scales as a function of plasma carbon content. The proposed reasons for these shock and acoustic trends are discussed, which include particle size and morphology, surface impurities, and dispersion and flow within the plasma.

Comparative analysis of ChAdOx1 nCoV-19 and Ad26.COV2.S SARS-CoV-2 vector vaccines.

Vector-based SARS-CoV-2 vaccines have been associated with vaccine- induced thrombosis with thrombocytopenia syndrome (VITT/TTS), but the causative factors are still unresolved. We comprehensively analyzed the ChAdOx1 nCoV-19 (AstraZeneca) and Ad26.COV2.S (Johnson & Johnson) vaccines. ChAdOx1 nCoV-19 contains significant amounts of host cell protein impurities, including functionally active proteasomes, and adenoviral proteins. A much smaller amount of impurities was found in Ad26.COV2.S. Platelet factor 4 formed complexes with ChAdOx1 nCoV-19 constituents, but not with purified virions from ChAdOx1 nCoV-19 or with Ad26.COV2.S. Vascular hyperpermeability was induced by ChAdOx nCoV-19 but not by Ad26.COV2.S. These differences in impurities together with EDTAinduced capillary leakage might contribute to the higher incidence rate of VITT associated with ChAdOx1 nCoV-19 compared to Ad26.COV2.S.

Reproducibility warning: The curious case of polyethylene glycol 6000 and spheroid cell culture.

Reproducibility of results is essential for a well-designed and conducted experiment. Several reasons may originate failure in reproducing data, such as selective reporting, low statistical power, or poor analysis. In this study, we used PEG6000 samples from different distributors and tested their capability inducing spheroid formation upon surface coating. MALDI-MS, NMR, FTIR, and Triple SEC analysis of the different PEG60000s showed nearly identical physicochemical properties different, with only minor differences in mass and hydrodynamic radius, and AFM analysis showed no significant differences in the surface coatings obtained with the available PEG6000s. Despite these similarities, just one showed a highly reproducible formation of spheroids with different cell lines, such as HT-29, HeLa, Caco2, and PANC-1. Using the peculiar PEG6000 sample and a reference PEG6000 chosen amongst the others as control, we tested the effect of the cell/PEG interaction by incubating cells in the PEG solution prior to cell plating. These experiments indicate that the spheroid formation is due to direct interaction of the polymer with the cells rather than by interaction of cells with the coated surfaces. The experiments point out that for biological entities, such as cells or tissues, even very small differences in impurities or minimal variations in the starting product can have a very strong impact on the reproducibility of data.

Investigation of gettering effects in CZ-type silicon with SIMS

Ion implantation is a well-known standard procedure in electronic device technology for precise and controlled introduction of dopants into silicon. However, damage caused by implantation acts as effective gettering zones, collecting unwanted metal impurities. This effect can be applied for "proximity gettering" reducing the concentration of impurities in the active device region. In this study the consequences of high-energy ion implantation into silicon and of subsequent annealing were analysed by means of secondary ion mass spectrometry (SIMS). Depth profiles were recorded of such impurities as copper, oxygen and carbon to obtain information about their gettering behaviour. The differences in impurities gettering behaviour were studied as a function of the implanted ions, P and Si, of the implantation dose and annealing time at T = 900 degrees C. Besides impurities gettering at the mean projected range (Rp) of implanted ions, Rp-effect, defects at around half of the projected ion range, Rp/2-effect, and even in some cases beyond Rp, trans-Rp-effect, have also been found to be effective in gettering of material impurities.

SIMS investigation of gettering centres produced by phosphorus MeV ion implantation

The ion implantation is a well-known standard procedure in electronic device technology for precise and controlled introduction of dopants into silicon. Damages caused by implantation act as effective gettering zones, collecting unwanted metal impurities. In this work, the consequences of high-energy ion implantation into silicon and of subsequently annealing were analysed by means of secondary ion mass spectrometry (SIMS). The differences in impurities gettering behaviour were studied in dependence of the implantation dose and annealing time at T = 900 °C.

Achieving On-Aim Product Quality Control by Design

One important reason for delivering excellent dynamic performance in a new or existing process centers on the need to control product quality on-aim (defined as keeping product quality variables at a given target with low variability around that target). This consistency requirement is a particularly key issue for pharmaceuticals, food ingredients, specialty chemicals, monomers, polymers, fibers, etc., where it is often impossible to measure all properties and where small differences in impurities can cause a significant change in end-use characteristics. Achieving the ability to control product quality on-aim does not happen by accident, it happens by deliberate design. This paper summarizes an industrial view on incorporating controllability and developing plantwide control strategies at the stage where a new process is being designed. It presents several industrial examples to highlight key concepts.

Preliminary report on porcelain in Meissen (Germany) and Arita (Japan)

The Meissen and the Kakiemon-style Arita wares were investigated by PIXE and EPMA. Both porcelain matrices were characterized by high purity ceramics, which are white in tone and translucent due to small amounts of an iron oxide inclusion. From overglazed red, green and gilt parts, enrichment of Fe, Cu, and Au, respectively, was commonly found from the above two wares. There is a resemblance between these two wares in main chemical constituents but there is a difference in impurities or minor elements.

NMR Studies of Orientation-Dependent Nuclear Spin-Spin Relaxation and Lineshapes in 13C-Enriched Diamonds

The present paper is devoted to the NMR investigations of 13C-enriched diamonds. Two greenish samples with a small difference in impurities have been under investigation. Both orientation-dependent lineshape and spin-spin relaxation-time measurements as functions of crystal orientation were collected. By analysis of the orientation-dependent data, an interesting characteristic behavior of the values was obtained. It was found that the main features of these dependencies are due to the dipole-dipole interactions between the neighboring nuclei. Identification of the additional lineshape splitting caused by dipole-dipole interactions was supported by MAS experiments. Theoretical estimates of lineshape and spin-spin relaxation time for several crystal orientations within the simple five-nuclei model are found to be sufficiently accurate to obtain agreement with the experimental data.

Impurities in Commercial Saccharin. I. Impurities Soluble in Organic Solvents

Thirteen saccharin samples used for carcinogenicity tests in animals in various laboratories were analyzed for their chemical purity. Although most of the impurities were water-soluble, some were mainly soluble in organic solvents. These impurities were extracted with chloroform-methanol from a water solution of sodium saccharin. Samples obtained as acid-saccharin were converted to the sodium form before extraction. The major impurity in commercial saccharin, o-toluenesulfonamide, was also soluble in this system. Impurities were separated by gas-liquid chromatography of the underivatized, concentrated extract. Eleven major, well separated peaks were collected from the gas chromatographic column and identified by mass spectroscopy. Some of the peaks were compared with known standards. Qualitative and quantitative differences in impurities were observed among different saccharin samples. The identified impurities (in order of appearance from the gas-liquid chromatographic column) were as follows: o-toluenesulfonamide; p-toluenesufonamide; 1,2-benzisothiazole 1,1-dioxide; 1,2-benzisothiazoline 1,1-dioxide; diphenylsulfone; 0,0'-ditolylsulfone; o,m'-ditolylsulfone, o,p'-ditolylsulfone; m,p'-ditolylsulfone; p,p'-ditolylsulfone, and tetracosane.

A Study of Deproteinized Rubber

Abstract In Part I we assumed that deproteinized rubber would deteriorate more rapidly than washed smoked sheet. But the present experiments indicate that our supposition was not correct, because the former was more resistant than the latter to mechanical deterioration. The same result was true of the specially treated rubber. It can be assumed that this depends on differences in the aging of the rubber hydrocarbon itself. But for several reasons, it is more likely that the major causes are differences in impurities and uniformity of cure. From several reports concerning protein in crude rubber by Stevens and others (Stevens, Kolloid Z., 14, 91 (1914); Park and Sebrell, India-Rubber J., 73, 265 (1927); Pickles, Trans. Inst. Rubber Ind., 3, 60 (1927)), water-soluble protein would have an immense effect on deterioration. Depolymerization and disaggregation would be the cause of deterioration by the aging of vulcanized rubber. This depolymerization, especially in artificial aging, cannot be explained merely by oxidation of the unsaturated part of the molecules, but must be attributed also to oxidation of combined sulfur, the formation of hydrogen sulfide, oxidation or other change in the free sulfur, metallic salts, proteins, and abietic acid. It has already been shown that oxidizability increases with increase in the time of cure, and that there is no relation between oxidizability and optimum cure. It has also been found that addition of acid to rubber decreases the heat deterioration (unreported experiments). Moreover, it has been found that resistivity to deterioration is increased by smoking and that the most easily oxidizable mixes contain in the neighborhood of 7 per cent of combined sulfur (cf. Kohman, J. Phys. Chem., 31, 23 (1927)), lower percentages of combined sulfur resulting in greater resistance to deterioration (cf. Boggs, Ind. Eng. Chem., 22, 748 (1930)).