• 약학회지
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• 제58권4호
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• pp.255-261
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• 2014

Poly-pharmacy has been on the rise because of aging of population and chronic disease. Most of drug metabolism happens in the liver by CYP isozymes and the metabolism by CYP450 enzymes. The Cytochrome P450 (CYP) is a superfamily of enzymes that catalyzes the oxidations of many endogenous and exogenous compounds. Primary human Hepatocytes (HH) are considered as the gold standard model for In vitro drug interaction studies. However, there are several limitations (cost, limited life span) for using HH cells. HepaRG cells are being used as a possible alternative. HepaRG cells were cultured in William E medium containing the positive control inducers (1A2: 10, 25, 50 ${\mu}M$ omeprazole, 2C9 and 2C19: 10 ${\mu}M$ rifampin, 3A4: 10, 25, 50 ${\mu}M$ rifampin) at $37^{\circ}C$, 5 % $CO_2$ in a humidified atmosphere. This study was to evaluate the induction of CYP isozymes (1A2, 2C9, 2C19 and 3A4) using LC-MS/MS. We evaluated the potential induction ability of Bosentan, as a drug of pulmonary artery hypertension, in HepaRG cells. For reference, dose of the Bosentan is determined to the basis of the $C_{max}$ (835 mg/ml) value. The enzyme activity demonstrated that CYP2C9 and 3A4 were induced up to 20 times by Bosentan. Like as In vivo, the enzyme activity of CYP2C9 and CYP3A4 is significantly induced in a dose-dependent by Bosentan.

• 분석과학
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• 제28권2호
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• pp.86-97
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• 2015

Recently, the consumption of dietary supplements has increased because of people’s greater interest in health. Unfortunately, the sales of dietary supplements containing unauthorized substances such as drugs have also increased. We developed a rapid, accurate method for the simultaneous determination of antihistamines using liquid chromatography tandem mass spectrometry with a multiple reaction monitoring mode. The limit of detection (LOD) and limit of quantification (LOQ) of the instrument used in this method were in the ranges 0.0003-0.3 and 0.0009-0.6 µg mL⁻¹, respectively. The linearity of the method was > 0.99. The precision levels of the method were 0.1-9.8% (intra-day) and 0.3-9.6% (inter-day), and the levels of accuracy of the method were 82.7-115.0% (intra-day) and 84.3-113.0% (inter-day). The mean of recovery of the method was in the range of 83.9-117.9% and the RSD of the stability was less than 5.9%.

• Biomolecules & Therapeutics
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• 제25권3호
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• pp.288-295
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• 2017

The incidence of polypharmacy-which can result in drug-drug interactions-has increased in recent years. Drug-metabolizing enzymes and drug transporters are important polypharmacy modulators. In this study, the effects of bosentan and rifampin on the expression and activities of organic anion-transporting peptide (OATP) and cytochrome P450 (CYP450) 2C9 and CYP3A4 were investigated in vitro. HEK293 cells and primary human hepatocytes overexpressing the target genes were treated with bosentan and various concentrations of rifampin, which decreased the uptake activities of OATP transporters in a dose-dependent manner. In primary human hepatocytes, CYP2C9 and CYP3A4 gene expression and activities decreased upon treatment with $20{\mu}M$ $bosentan+200{\mu}M$ rifampin. Rifampin also reduced gene expression of OATP1B1, OATP1B3, and OATP2B1 transporter, and inhibited bosentan influx in human hepatocytes at increasing concentrations. These results confirm rifampin- and bosentan-induced interactions between OATP transporters and CYP450.

• 한국환경농학회지
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• 제33권4호
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• pp.388-394
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• 2014

이 연구는 농산물 중 아클로니펜의 안전관리를 위한 공정분석법을 확립하기 위하여 수행하였으며 분석법의 선택성, 검출한계 및 정량한계, 회수율에 대한 검증을 통하여 아클로니펜의 공정시험법으로의 유효성을 확인하였다. 아클로니펜의 이화학적 특징에 따라 분석기기는 GC-ECD를 사용하였고, 아세톤 추출 후 실리카 카트리지를 이용하여 정제하였다. 개발된 분석법의 회수율은 고추에서 92.3-95.0%, 감귤에서 74.3-90.4%, 아몬드에서 76.7-89.8%였으며, 분석오차는 8%이하로 코덱스 가이드라인 (CAC/GL 40)에 적합하였다. 또한 GC-MS를 이용한 재확인 과정을 통해 분석법의 신뢰성을 확보하였다. 따라서 본 분석법의 정확성 및 재현성이 입증되어 농산물 중 아클로니펜의 잔류분석에 적용할 수 있을 것으로 판단된다.

• 한국식품위생안전성학회지
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• 제38권3호
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• pp.79-88
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• 2023

Trifludimoxazin은 triazinone 계열 제초제로 프로토포르 피리노겐-IX 산화효소(protoporphyrinogen oxidase, PPO)를 억제하며 벼와 광엽 잡초를 방제하는 데 사용된다. PPO의 결핍은 세포막의 손상을 일으켜 식물을 시들게 한다. Trifludimoxazin의 농산물 중 잔류허용기준은 미국에서 아몬드에 대하여 0.15 mg/kg, 땅콩 등 9종에 대하여 0.01 mg/kg으로 설정되어있으며, 모화합물을 잔류물의 정의로 설정하여 관리하고 있다. 코덱스(CODEX), 유럽(EC) 일본(JFCRF)에서는 잔류허용기준(MRL)과 잔류물의 정의가 설정되어 있지 않다. 호주(APVMA)에서는 trifludimoxazin과 대사체 M850H001의 합을 잔류물의 정의로 설정하였으며, MRL은 보리와 밀에 0.01 mg/kg으로 설정되어 있다. 국내에서 신규 등록 예정임에 따라 본 연구에서는 농산물 중 trifludimoxazin의 잔류량을 분석하기 위한 공정시험법을 마련하고자 하였다. Trifludimoxazin의 물리 화학적 특성을 고려하여 아세토니트릴을 추출용매로 사용하는 Quick, easy, cheap, effective, rugged and safe (QuEChERS)법을 이용하여 추출 및 정제조건을 확립한 후 LC-MS/MS를 분석기기로 선정하였다. Trifludimoxazin의 결정계수(R²)는 모두 0.99 이상으로 우수하였으며 정량한계는 0.01 mg/kg으로 나타났다. 대표 농산물 5종(현미, 감자, 대두, 감귤, 고추)에 대하여 정량한계, 정량한계 10배, 정량한계 50배 수준으로 처리하여 회수율 실험을 한 결과 평균 회수율은(5반복) 73.5-85.3%로 나타났으며, 상대 표준편차(RSD)는 3.8% 이하로 나타났다. 본 연구는 국제식품규격위원회 농약 분석법 가이드라인의 잔류농약 분석 기준 및 식품의약품안전평가원의 식품등 시험법 마련 표준절차에 관한 가이드라인(2016)에 적합한 수준이며, 향후 공정시험법으로 활용될 예정이다. 본 연구에서 개발한 시험법에 대해 농산물 125건을 대상으로 잔류농약 모니터링을 한 결과 trifludimoxazin의 잔류량이 확인되지 않았다.

• 대한안전경영과학회지
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• 제7권1호
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• pp.11-23
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• 2005

It is difficult to put it into practice in that it requires bearing too much burden to draw out the planning itself in a case of large construction work. Consequently in this paper we select evaluation criteria by construction progress, classify into several categories, and regard potential danger which often occurs, as a evaluation criterion. Further step is to allow workers or collaborated companies to express their expert opinions or experiences and to encourage quality and process control and autonomous safety control by applying PSM(Process Safety Management) method using AHP(Analytic Hierarchy Process) and to development of PSIM(Process Safety Information Management) evaluation method in the construction. The reason why PSIM method should be quantitative and substantial progress is because it contributes Korean constructing companies to enhancing their safety control ability and to taking an equal stance just like developed countries, thereby strengthening their competitive edges.

• 생약학회지
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• 제41권2호
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• pp.136-140
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• 2010

This study was carried out to utilize non-toxic solvents instead of harmful solvents for the TLC(Thin Layer Chromatography) identification test of herbal medicines. It is recommended not to use harmful solvent such as chloroform at a viewpoint of clean analysis. In this study, we revised the identification test of 10 items in the Korea Pharmacopoeia(KP) and the Korean Herbal Pharmacopoeia(KHP) such as Cornus officinalis S. containing the harmful solvents on the developing solvent and established identification test that is utilized non-toxic solvents by HPTLC(High Performance Thin Layer Chromatography).

• 생약학회지
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• 제41권4호
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• pp.297-302
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• 2010

Lophatheri Herba is the aerial part of Lophatherum gracile Bronghiart(淡竹葉, Gramineae). 25~75 cm in length. Stem: cylindrical with nodes, empty inside, externally pale yellowish green. Leaf: dehiscent of lanceolate lamina, shrunken and rolled, 5~20 cm long, 10~35 mm wide; surface: pale green ~ yellowish green, parallel-formed with veins of square reticulate, more distinct of appearance on the lower surface. Banbusae Caulis In Taeniam is the stringy strip derived from the stem with the peeled-off epidermis of Phllostachys nigra Munro var. henosis Stapf, and Phllostachys bambusoides Siebold et Zuccarini(竹葉, Gramineae). Irregular in size and shape, thin plane ~ strip-shaped, sometimes powdery, sometimes 1~3 mm thick. Outer surface: pale green ~ yellowish green, sometimes grayish white L. gracile and P. nigra have different origins although they show similar morphologic features. We were able to distinguish between L. gracile and P. nigra which are almost indistinguishable through this study. AFLP(Amplifide Fragment Length Polymorphism) was more suitable for identifying differences between L. gracile and P. nigra in comparison with other genetic analysis using chemical analysis. Therefore. molecular biological methods are believed to be useful for discovering origins of herbal medicines.

• Bulletin of the Korean Chemical Society
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• 제34권4호
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• pp.1131-1136
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• 2013

Parabens, the esters of p-hydroxybenzoic acid, have been widely used as antimicrobial preservatives in cosmetic products, drugs, and processed foods and beverages. However, some parabens have been shown to have weak estrogenic effects through in vivo and in vitro studies. Because such widespread use has raised concerns about the potential human health risks associated with exposure to parabens, we developed a simultaneous analytical method to quantify 4 parabens (methyl, ethyl, propyl, and butyl) in human urine, by using solid-phase extraction and high-performance liquid chromatography coupled with triple quadrupole mass spectrometry. This method showed good specificity, linearity ($R^2$ > 0.999), accuracy (92.2-112.4%), precision (0.9-9.6%, CV), and recovery (95.7-102.0%). The LOQs for the 4 parabens were 1.0, 0.5, 0.2, and 0.5 ng/mL, respectively. This method could be used for quick and accurate analysis of a large number of human samples in epidemiological studies to assess the prevalence of human exposure to parabens.

• Mass Spectrometry Letters
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• 제10권2호
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• pp.43-49
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• 2019

The aim of this study was conducted to develop an analytical method to determine the concentration of ceftiofur residue in eel, flatfish, and shrimp. For derivatization and extraction, the sample was hydrolyzed with dithioerythritol to produce desfuroylceftiofur, which was then derivatized by iodoacetamide to obtain desfuroylceftiofur acetamide. For purification, the process of solid phase extraction (Oasis HLB) was used. The target analytes were confirmed and quantified in $C_{18}$ column using liquid chromatography-tandem mass spectrometry with 0.1% formic acid in water (A) and 0.1% formic acid in acetonitrile (B) as the mobile phase. The linearity of the standard calibration curve was confirmed by a correlation coefficient, $r^2>0.99$. The limit of quantification for ceftiofur was 0.002 mg/kg; the accuracy (expressed as the average recoveries) was 80.6-105%; the precision (expressed as the coefficient of variation) was below 6.3% at 0.015, 0.03, and 0.06 mg/kg. The validated method demonstrated high accuracy and acceptable sensitivity to meet the Codex guideline requirements. The developed method was tested using market samples. As a results, ceftiofur was detected in one sample. Therefore, it can be applied to the analysis of ceftiofur residues in fishery products.