• 분석과학
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• 제36권4호
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• pp.180-190
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• 2023

The presence of process related impurities in any drug or the drug product was associated with its safety, stability and efficacy. The overall literature survey proved that there is no method published on the assessment of process related impurities in brigatinib. In this study, a simple, reliable and stable HPLC qualitative method was reported for quantification of process related impurities with easy and quick extraction procedure. The impurities along with standard brigatinib was resolved on Lichrospher^® C18 (250 mm × 4.6 mm; 5 ㎛ particle size) column in room temperature using methanol, acetonitrile, pH 4.5 phosphate buffer in 55:25:20 (v/v) at 1.0 mL/min as mobile phase and UV detection at 261 nm. The method produces well resolved peaks at retention time of 4.60 min, 12.28 min, 3.37 min, 7.34 min and 8.39 min respectively for brigatinib, impurity A, B, C and D. The method produces a very sensitive detection limit of 0.0065 ㎍/mL, 0.0068 ㎍/mL, 0.0053 ㎍/mL and 0.0058 ㎍/mL for impurity A, B, C and D respectively with calibration curve linear in the concentration range of 22.5-135 ㎍/mL for brigatinib and 0.0225-0.135 ㎍/mL for impurities. The method produces all the validation parameters under the acceptable level and doesn't produces any considerable changes in peak area response while minor changes in the developed method conditions. The method can effectively resolve the unknown stress degradation products along with known impurities with less % degradation. The method can efficiently resolve and quantify the impurities in formulation and hence can suitable for the routine quality analysis of brigatinib in raw material and formulation.

• 분석과학
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• 제37권1호
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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.

• 한국산학기술학회논문지
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• 제14권8호
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• pp.3597-3601
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• 2013

본 연구에서는 고품질의 합성다이아몬드를 얻고자 합성다이아몬드 표면에 잔류하는 그래핀, DLC 등의 흑연계 준안정상을 효과적으로 제거하는 세정공정을 위해 왕수와 황산 외에 $K_2S_2O_8$, $P_2O_5$, $KMnO_4$의 산화제가 들어간 습식세정공정, P II 제안하였다. 이 공정은 기존의 산처리를 이용한 세정공정(P I) 뿐만 아니라 신세정공정(P I+P II)을 함께 사용하여 7GPa-$1500^{\circ}C$-5minutes의 조건 하에서 합성된 200um의 다이아몬드 표면에 잔류하는 흑연과 불순물 등을 제거하기 위해 진행되었다. 이를 육안분석, 광학현미경, 마이크로라만, TGA-DTA를 통하여 확인하였다. 육안분석과 광학현미경 분석 결과 새로운 습식세정공정(P I+P II) 진행 후 합성다이아몬드의 채색이 밝은 노란색으로 개선되었다. 또한 마이크로라만 분석을 통해 $1330cm^{-1}$의 다이아몬드 고유 피크 외에 $1440cm^{-1}$의 흑연계 준안정상인 DLC피크가 사라지는 것을 확인하여 정량적으로 잔류불순물의 양이 줄어든 것을 확인하였다. TGA-DTA 결과, 처리 전(P I only) 흑연계 준안정상이 먼저 분해되어 $770.91^{\circ}C$부터 열분해가 시작되었으나 신세정공정(P I+P II)으로 처리 후 순수한 합성다이아몬드는 $892.18^{\circ}C$부터 시작되어 흑연계 준안정상이 효과적으로 제거된 것을 확인하였다. 이러한 신세정공정은 합성다이아몬드의 잔류불순물제거를 통해 품질향상을 기대할 수 있었다.

• 분석과학
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• 제32권6호
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• pp.225-232
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• 2019

Traceability establishment in chemical measurements is a like a linkage established through an unbroken chain from the measured results to the international system (SI) of units. The primary process for traceability establishment is the purity assignment of a target material to be measured. In this study, we studied the purity assignment of 17α-hydroxyprogesterone (17-OHP). The presence of 17-OHP is indicative of congenital adrenal hyperplasia (CAH) and it builds up due to the deficiency of 21-hydroxylase and 11β-hydroxylase enzyme in the human blood. The purity assignment of 17-OHP was performed by the mass balance method, in which the impurities are categorized into four classes: total related structural impurities, water, residual organic solvents, and nonvolatiles/inorganics. The total related structural impurities were characterized by HPLC-UV; water content was determined by Karl-Fisher coulometer; and the total residual solvents and nonvolatiles/inorganics were determined by TGA. The purity of 17-OHP from a commercial manufacturer was calculated as 993.30 mg/g, and the expanded uncertainty was 0.58 mg/g. The proposed method was validated by uncertainty evaluation and comparing with the actual value of purity.

• 한국재료학회지
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• 제20권12호
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• pp.645-648
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• 2010

The structure and morphology of epitaxial layer defects in epitaxial Si wafers produced by the Czochralski method were studied using focused ion beam (FIB) milling, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Epitaxial growth was carried out in a horizontal reactor at atmospheric pressure. The p-type Si wafers were loaded into the reactor at about $800^{\circ}C$ and heated to about $1150^{\circ}C$ in $H_2$. An epitaxial layer with a thickness of $4{\mu}m$ was grown at a temperature of 1080-$1100^{\circ}C$. Octahedral void defects, the inner walls of which were covered with a 2-4 nm-thick oxide, were surrounded mainly by $\{111\}$ planes. The formation of octahedral void defects was closely related to the agglomeration of vacancies during the growth process. Cross-sectional TEM observation suggests that the carbon impurities might possibly be related to the formation of oxide defects, considering that some kinds of carbon impurities remain on the Si surface during oxidation. In addition, carbon and oxygen impurities might play a crucial role in the formation of void defects during growth of the epitaxial layer.

• 한국재료학회지
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• 제28권4호
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• pp.247-253
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• 2018

We examined the characteristics of indium tin zinc oxide (ITZO) thin film transistors (TFTs) on polyimide (PI) substrates for next-generation flexible display application. In this study, the ITZO TFT was fabricated and analyzed with a SiOx/SiNx gate insulator deposited using plasma enhanced chemical vapor deposition (PECVD) below $350^{\circ}C$. X-ray photoelectron spectroscopy (XPS) and secondary ion mass spectroscopy (SIMS) results revealed that the oxygen vacancies and impurities such as H, OH and $H_2O$ increased at ITZO/gate insulator interface. Our study suggests that the hydrogen related impurities existing in the PI and gate insulator were diffused into the channel during the fabrication process. We demonstrate that these impurities and oxygen vacancies in the ITZO channel/gate insulator may cause degradation of the electrical characteristics and bias stability. Therefore, in order to realize high performance oxide TFTs for flexible displays, it is necessary to develop a buffer layer (e.g., $Al_2O_3$) that can sufficiently prevent the diffusion of impurities into the channel.

• 분석과학
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• 제37권2호
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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.

• Tribology and Lubricants
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• 제23권4호
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• pp.143-148
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• 2007

The surface defects of an aluminum tube for an OPC drum have been analyzed using a scanning microscopy(SEM) and an energy dispersive X-ray analyze.(EDX). The SEM/EDX system, which may provide good information on the surface defects and their distributions, provides an optical diameter of an impurity and a chemical composition. These are strongly related on the coated film thickness and quality of an OPC drum, which is a key element of a toner cartridge for a laser printer. The experimental results show that the local deformations, scratch wear, and flaws are produce the non-uniform coating layers, which may be removed by a manufacturing process of an aluminum tube. The major parameters on the coating quality of an OPC drum are the impurities of an aluminum tube such as silicon, oxygen, calcium, carbon, sulphur, chlorine, and others. These impurities may be removed by an ingot molding, extrusion and drawing, quality control, and packing processes with a strict manufacturing technology.

• 한국응용과학기술학회지
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• 제25권4호
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• pp.503-510
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• 2008

This research is related to the process of refining the raw material, industrial 2-propanone to the 2-propanone of the electronic grade. With this view, the high purity of 2-propanone was obtained through the complex preprocessing(physical adsorption method), distillation process and membrane-filtration of distillate. Impurities were identified by GC and UV, and then we assayed the water content in 2-propanone passing adsorption step made of activated carbon and Zeolite 4A. Furthermore, the distillation was performed with the packed column distillation apparatus to eliminate impurities such as acetaldehyde. Particulates were removed by reduced-pressure filtration through $0.5{\mu}m$ membrane filter and the number of the particulates was measured by particulate counter to confirm the removal of impure particles.

• 분석과학
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• 제30권5호
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• pp.226-233
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• 2017

In general, quantitative chemical analysis in various areas including food, the environment, in vitro diagnostics, etc., requires traceability in order to increase the reliability of the measurements. Measurement traceability is a property of an unbroken chain of comparisons relating an instrument's measurements to SI units. Purity analysis is the first process for establishing traceability to SI units in chemical measurements. The purpose of this study is to develop and validate a method of purity assignment for establishing the traceability of $17{\beta}$-estradiol measurements in an in vitro diagnostics field. The establishment of this method is very important as it can be applied to the development of CRM and to the analysis of the purity of other hormones. The method of assignment of the purity of $17{\beta}$-estradiol was developed using the mass balance method and was validated through participation in an International comparison. In the mass balance method, impurities are categorized into four classes as follows: total related structure impurities, water, residual organic solvents, and nonvolatiles/inorganics. In this study, total related structure impurities were characterized by a gas chromatography-flame ionization detector (GC-FID) and a high-performance liquid chromatography-ultraviolet (HPLC-UV) detector, water content was determined by a Karl-Fisher coulometer, and total residual solvents and nonvolatiles/inorganics were checked simultaneously by thermogravimetric analysis (TGA). The purity of the $17{\beta}$-estradiol was 985.6 mg/g and the expanded uncertainty was 2.1 mg/g at 95% confidence. The developed method can be applied to the development of certified reference materials, which play a critical role in traceability.