• Analytical Science and Technology
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• v.37 no.5
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• pp.280-294
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• 2024

This study introduces a novel analytical method for the assessment of pralsetinib impurities and degradation products (DPs), addressing critical gaps in existing methodologies. This research aims to develop a robust HPLC method for impurity analysis, characterize degradation products using LC-MS, and evaluate the environmental impact of the method. The study began by optimizing HPLC conditions with various columns and buffers, ultimately achieving successful separation using an XBridge^® RP-C18 column with ethanol as solvent A and 50 mM formic acid at pH 2.9. This setup provided excellent peak resolution and symmetry, essential for reliable stability studies. The developed HPLC method was then adapted for HPLC-MS/MS, enhancing sensitivity and detection efficiency of DPs. Stress degradation studies of pralsetinib under different conditions (acidic, basic, oxidative, thermal, and photolytic) revealed significant degradation under acidic (29.3 %) and basic (21.5 %) conditions, with several DPs identified. Oxidative stress resulted in 19.8 % degradation, while thermal and photolytic conditions caused minimal degradation. HPLC-MS/MS analysis identified structures of five degradation products, providing detailed insights into pralsetinib's stability and degradation pathways. Method validation followed ICH guidelines Q2(R1), confirming method's specificity, selectivity, sensitivity, linearity, accuracy, precision, and robustness. The method exhibited strong linearity with a coefficient of determination (r²) greater than 0.999 for pralsetinib and its impurities. This method advances impurity detection and DPs characterization, ensuring the quality and safety of pralsetinib. Additionally, method's environmental impact was assessed, aligning with sustainable analytical practices. These findings provide essential data on pralsetinib's stability, guiding storage conditions and ensuring its efficacy and safety in pharmaceutical applications.

• Journal of Applied Reliability
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• v.13 no.2
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• pp.87-98
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• 2013

Accelerated degradation tests (ADTs) measuring failure-related degradation characteristic at the accelerated condition are widely used to assess the reliability of highly reliable products. Often, however, little degradation could be observed even in single-stress ADTs due to the high reliability of test unit, and as a result poor estimate of the reliability may be obtained. ADTs with multiple stress variables can be employed to overcome such difficulties. In this paper, optimal ADT plans with two stress variables are developed assuming that the degradation characteristic follows Weibull distribution by determining the stress levels, the proportion of test units allocated to each stress level such that the asymptotic variance of the maximum likelihood estimator of the q-th quantile of the lifetime distribution at the use condition is minimized.

• Analytical Science and Technology
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• v.37 no.2
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• pp.98-113
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• 2024

The current investigation entails the characterization of five degradation products (DPs) formed under different stress conditions of loteprednol using liquid chromatography-tandem mass spectrometry (LC-MS/MS). In addition, this study developed a stable high-performance liquid chromatography (HPLC) method for evaluating loteprednol along with impurities. The method conditions were meticulously fine-tuned which involved the exploration of the appropriate solvent, pH, flow of the mobile phase, columns, and wavelength. The method conditions were carefully chosen to successfully resolve the impurities of loteprednol and were employed in subsequent validation procedures. The stability profile of loteprednol was exposed to stress degradation experiments conducted under five conditions, and DPs were structurally characterized by employing LC-MS/MS. The chromatographic resolution of loteprednol and its impurities along with DPs was effectively achieved using a Phenomenex Luna 250 mm C18 column using 0.1 % phosphoric acid, methanol, and acetonitrile in 45:25:30 (v/v) pumped isocratically at 0.8 mL/min with 243 nm wavelength. The method produces an accurate fit calibration curve in 50-300 ㎍/mL for loteprednol and LOQ (0.05 ㎍/mL) - 0.30 ㎍/mL for its impurities with acceptable precision, accuracy, and recovery. The stress-induced degradation study revealed the degradation of loteprednol under basic, acidic, and photolytic conditions, resulting in the formation of seven distinct DPs. The efficacy of this method was validated through LC-MS/MS, which allowed for the verification of the chemical structures of the newly generated DPs of loteprednol. This method was appropriate for assessing the impurities of loteprednol and can also be appropriate for structural and quantitative assessment of its degradation products.

• International Journal of Reliability and Applications
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• v.17 no.1
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• pp.21-49
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• 2016

Many mechanical, electrical and electronic products have more than one performance characteristics (PCs). For example the performance degradation of rubidium discharge lamps can be characterized by the rubidium consumption or the decreasing intensity the lamp. The product may degrade due to all the PCs which may be independent or dependent. This paper deals with the design of optimal bivariate step-stress partially accelerated degradation test (PADT) with degradation paths modelled by gamma process. The dependency between PCs has been modelled through Frank copula function. In partial step-stress loading, the unit is tested at usual stress for some time, and then the stress is accelerated. This helps in preventing over-stressing of the test specimens. Failure occurs when the performance characteristic crosses the critical value the first time. Under the constraint of total experimental cost, the optimal test duration and the optimal number of inspections at each intermediate stress level are obtained using variance optimality criterion.

• Analytical Science and Technology
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• v.37 no.1
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• pp.25-38
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• 2024

The study aimed to investigate a novel approach by utilizing liquid chromatography (LC) and liquid chromatography-mass spectrometry (LC-MS) to separate, identify and characterize very nominal quantities of degradation products (DPs) of balsalazide along with its process related impurities without isolation from their reaction mixtures. The impurities along with balsalazide were resolved on spherisorb ODS2 (250×4.6 mm, 5.0 ㎛) column at room temperature using 0.2 M sodium acetate solution at pH 4.5 and methanol in the ratio of 55:45 (v/v) as mobile phase pumped isocratically at 1.0 mL/min as mobile phase and UV detection at 255 nm. The method shows sensitive detection limit of 0.003 ㎍/mL, 0.015 ㎍/mL and 0.009 ㎍/mL respectively for impurity 1, 2 and 3 with calibration curve liner in the range of 50-300 ㎍/mL for balsalazide and 0.05-0.30 for its impurities. The balsalazide pure compound was subjected to stress studies and a total of four degradation products (DPs) were formed during the stress study and all the DPs were characterized with the help of their fragmentation pattern and the masses obtained upon LC-MS/MS. The DPs were identified as 3-({4-[(E)-(4-hydroxyphenyl) diazenyl]benzoyl}amino)propanoic acid (DP 1), 4-[(E)-(4-hydroxyphenyl)diazenyl] benzamide (DP 2), 5-[(E)-(4-carbamoylphenyl)diazenyl]-2-hydroxybenzoic acid (DP 3) and 3-({4-[(E)-phenyldiazenyl]benzoyl}amino)propanoic acid (DP 4). Based on findings, it was concluded that, the proposed method was successfully applicable for routine analysis of balsalazide and its process related impurities in pure drug and formulations and also applicable for identification of known and unknown impurities of balsalazide.

• Journal of Korean Society for Quality Management
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• v.40 no.2
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• pp.117-125
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• 2012

For the highly reliable products, an accelerated degradation test (ADT) is a useful tool which has been employed in industry to obtain reliability-related information within an affordable amount of time and cost. In an ADT, as all other reliability tests, it is important to carefully design the ADT beforehand to obtain estimates of the quantities of interest as precisely as possible. In this paper, optimal ADTs are developed assuming that the constant-stress loading method is employed and the degradation characteristic follows a Wiener process. Under the constraint that the total cost does not exceed a pre-specified budget, the stress levels, the number of test units allocated to each stress level and the number of measurement (termination time) are determined such that the asymptotic variance of the maximum likelihood estimator of the q-th quantile of the lifetime distribution at the use condition is minimized.

• Journal of Dairy Science and Biotechnology
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• v.16 no.2
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• pp.137-153
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• 1998

It is found that many kinds of spices and herbs have a deodorization, acrid, coloration, antimicrobial or antioxidant effect. They also have physiological actions such as antiaging effect, anticancer effect, endurance enhancement, or stress degradation. Therefore, development of the dairy products with those above benefical effects of natural spices and herbs is necessary, and the functional dairy products which has an anticancer, antiobesity or coelenterate will be useful foods, especially patients.

• Journal of Korean Society of Industrial and Systems Engineering
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• v.38 no.4
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• pp.142-148
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• 2015

Due to advancements in technology and manufacturing capability, it is not uncommon that life tests yield no or few failures at low stress levels. In these situations it is difficult to analyse lifetime data and make meaningful inferences about product or system reliability. For some products or systems whose performance characteristics degrade over time, a failure is said to have occurred when a performance characteristic crosses a critical threshold. The measurements of the degradation characteristic contain much useful and credible information about product or system reliability. Degradation measurements of the performance characteristics of an unfailed unit at different times can directly relate reliability measures to physical characteristics. Reliability prediction based on physical performance measures can be an efficient and alternative method to estimate for some highly reliable parts or systems. If the degradation process and the distance between the last measurement and a specified threshold can be established, the remaining useful life is predicted in advance. In turn, this prediction leads to just in time maintenance decision to protect systems. In this paper, we describe techniques for mapping product or system which has degrading performance parameter to the associated classical reliability measures in the performance domain. This paper described a general modeling and analysis procedure for reliability prediction based on one dominant degradation performance characteristic considering pseudo degradation performance life trend model. This pseudo degradation trend model is based on probability modeling of a failure mechanism degradation trend and comparison of a projected distribution to pre-defined critical soft failure point in time or cycle.

• Molecules and Cells
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• v.45 no.12
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• pp.869-876
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• 2022

Methylglyoxal (MG) is a dicarbonyl compound formed in cells mainly by the spontaneous degradation of the triose phosphate intermediates of glycolysis. MG is a powerful precursor of advanced glycation end products, which lead to strong dicarbonyl and oxidative stress. Although divergent functions of MG have been observed depending on its concentration, MG is considered to be a potential antitumor factor due to its cytotoxic effects within the oncologic domain. MG detoxification is carried out by the glyoxalase system. Glyoxalase 1 (Glo1), the ubiquitous glutathionedependent enzyme responsible for MG degradation, is considered to be a tumor promoting factor due to it catalyzing the removal of cytotoxic MG. Indeed, various cancer types exhibit increased expression and activity of Glo1 that closely correlate with tumor cell growth and metastasis. Furthermore, mounting evidence suggests that Glo1 contributes to cancer stem cell survival. In this review, we discuss the role of Glo1 in the malignant progression of cancer and its possible use as a promising therapeutic target for tumor therapy. We also summarize therapeutic outcomes of Glo1 inhibitors as prospective treatments for the prevention of cancer.

• Journal of The Korean Society of Agricultural Engineers
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• v.65 no.4
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• pp.45-52
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• 2023

This study was conducted to examine the possibility of use as a structural material for ginseng cultivation facilities of recycled plastics. In order to determine the possibility that recycled plastic can replace timber used as a structural material for ginseng cultivation facilities, the specimens collected by elapsed time were compared with timber through bending tests. In addition, in order to analyze the effect of external environmental conditions on recycled plastic products, bending test was conducted with the specimens that had completed weathering test and accelerated heat aging test respectively. As a result, the bending strength of recycled plastic specimens with the elapsed time of 360 days was lower than that of timber. But bending strength of recycled plastic specimens exceeded the design allowable stress standard set by the Korea design standard (MOLIT, 2016). There was no degradation in quality of recycled plastic due to the external environment, and it was found that there would be no problem even if it was used as a structural material for ginseng cultivation facilities.