• Journal of Pharmaceutical Investigation
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• v.35 no.6
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• pp.423-429
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• 2005

A selective and sensitive reversed-phase HPLC method for the determination of fenoprofen in human serum was developed, validated, and applied to the pharmacokinetic study of fenoprofen calcium. Fenoprofen and internal standard, ketoprofen, were extracted from human serum by liquid-liquid extraction with diethyl ether and analyzed on a Luna C18(2) column with the mobile phase of acetonitrile-3 mM potassium dihydrogen phosphate (32:68, v/v, adjusted to pH 6.6 with phosphoric acid). Detection wavelength of 272 nm and flow rate of 0.25 mL/min were fixed for the study. The assay robustness for the changes of mobile phase pH, organic solvent content, and flow rate was confirmed by $3^{3}$ factorial design using a fixed fenoprofen concentration $(2\;{\mu}g/mL)$ with respect to its peak area and retention time. And also, the ruggedness of this method was investigated at three different laboratories using same quality control (QC) samples. This method showed linear response over the concentration range of $0.05-100\;{\mu}g/mL$ with correlation coefficients greater than 0.999. The lower limit of quantification using 1 mL of serum was $0.05\;{\mu}g/mL$, which was sensitive enough for pharmacokinetic studies. The overall accuracy of the quality control samples ranged from 92.27 to 109.20% for fenoprofen with overall precision (% C.V.) being 5.51-11.71 %. The relative mean recovery of fenoprofen for human serum was 81.7%. Stability (freeze-thaw, short and long-term) studies showed that fenoprofen was not stable during storage. But, extracted serum sample and stock solution were allowed to stand at ambient temperature for 12 hr prior to injection without affecting the quantification. The peak area and retention time of fenoprofen were not significantly affected by the changes of mobile phase pH, organic solvent content, and flow rate under the conditions studied. This method showed good ruggedness (within 15% C.V.) and was successfully used for the analysis of fenoprofen in human serum samples for the pharmacokinetic studies of orally administered Fenopron tablet (600 mg as fenoprofen) at three different laboratories, demonstrating the suitability of the method.

• Analytical Science and Technology
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• v.26 no.4
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• pp.221-227
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• 2013

A sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed for the investigation of the ginsenoside Rg1 in human plasma. After addition of internal standard (digoxin), plasma was diluted with acetone and methanol (80:20), the supernatant was concentrated and analyzed by LC-MS/MS. The optimal chromatographic separation was achieved on an Agilent Eclipse XDB-C18 column ($4.6{\times}150mm$, $5{\mu}m$) with a mobile phase of 0.1% formic acid in water and 0.1% formic acid in methanol at a flow rate of 0.9 mL/min gradient mode. The standard calibration curve for ginsenoside Rg1 was linear ($r^2=0.9995$) over the concentration range 1~500 ng/mL in human plasma. The intra- and inter-day precision over the concentration range of ginsenoside Rg1 was lower than 7.53% (correlation of variance, CV), and accuracy exceeded 98.28%. This LC-MS/MS assay of ginsenoside Rg1 in human plasma is applicable for quantifying in the pharmacokinetic study.

• Korean Journal of Clinical Pharmacy
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• v.16 no.1
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• pp.23-27
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• 2006

Doxorubicin (DXR) is a type of anti-cancer drug called an 'anthracycline glycoside', It works by impairing DNA synthesis, a crucial feature of cell division, and thus is able to target rapidly dividing cells. Doxorubicin is a very serious anti-cancer medication with definite potential to do great harm as well as great good. A liquid chromatography-tandem mass spectroscopy (LC-MS/MS) method was developed to identify and quantify DXR in small-volume biological samples. After the addition of internal standard (IS, $5{\mu}L\;of\;1{\mu}M/ml$ daunorubicin methanol solution) into the serum sample, the drug and IS were extracted by methanol. Following vortex for a 1min and centrifugation at 15,000g for 10 min the organic phase was transferred and evaporated under a vacuum. The residue was reconstituted with $350{\mu}L$ of mobile phase and $10{\mu}L$ was injected into C18 column with mobile phase composed of 0.05M ammonium acetate (0.1 M acetic acid adjusted to pH 3.5) and acetonitrile (40:60, v/v). The flow rate was kept constant at $350{\mu}L/min$. The ions were quantified in the multiple reaction mode (MRM), using positive ions, on a triple quadrupole mass spectrometer. The lower limits of quantification for Doxorubicin in plasma and small tissues were approximately 0.5 ng/mL and 0.5 ng/mL respectively. Intra- and inter-assay accuracy (% of nominal concentration) and precision (% CV) for all analytes were within 15%, respectively.

• Journal of Pharmaceutical Investigation
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• v.41 no.3
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• pp.191-196
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• 2011

In this study simple and sensitive high performance liquid chromatographic method using a commercially available column, was developed and validated for the determination of zolpidem tartrate in human plasma. The developed method with suitable validation was applied to a bioequivalence study of two different kinds of zolpidem tartrate. Two different formulations containing 10 mg of zolpidem tartate (CAS : 99294-93-6) were compared in 24 healthy male volunteers in order to compare the bioavailability and prove the bioequivalence. The study was performed in an open, single dose randomized, 2-sequence, cross-over design in 24 healthy male volunteers with a one-week washout period. Blood samples for pharmacokinetic profiling were drawn at selected times during 12 h. The mean $AUC_{0-12h}$, $C_{max}$, $T_{max}$ and $T_{1/2}$ were $676.6{\pm}223.4$ $ng{\cdot}h{\cdot}mL^{-1}$, $177.4{\pm}34.2$ $ng{\cdot}mL^{-1}$, and $0.8{\pm}0.4$ and $3.5{\pm}2.1$, respectively, for the test formulations, and $640.7{\pm}186.6$ $ng{\cdot}h{\cdot}mL^{-1}$, $193.0{\pm}64.5$ $ng{\cdot}mL^{-1}$, and $0.9{\pm}0.4$ and $2.7{\pm}0.9$, respectively, for the reference formulation. Both primary target parameters $AUC_{0-12h}$ and $C_{max}$ were log-transformed and tested parametrically by analysis of variance (ANOVA). 90% confidence intervals of $AUC_{0-12h}$ and $C_{max}$ were in the range of acceptable limits of bioequivalence (80-125%). Based on these results, the two formulations of zolpidem tartate are considered to be bioequivalent.

• YAKHAK HOEJI
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• v.57 no.2
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• pp.87-94
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• 2013

An analytical methodology based on solid-space extraction (SPE) with with Bond Elut Certify cartridge (Varian, 130 mg) has been developed for the qualification and quantitation of strychnine in blood. After the elution layer was evaporated, the residue was reconstituted with methanol for GC/MS. Internal standard was used 10 mg/l dextromethorphan. Strychnine is a potent central nervous stimulant and convulsant, and an alkaloid found in seeds of Strychnos nux-vomica. It was used therapeutically to improve circulation and muscle tone in oral or intramuscular doses of 0.05~8 mg. The fatal dose of strychnine for humans is 50~100 mg. A man was found dead lying curled up the corner of the large room in a roof house after the fire fighter opened a locked door inside to put out the fire. The postmortem blood and gastric contents were analyzed for toxicological testing. Strychnine and brucine were detected using GC/MS first in gastric contents extracts. The contents of strychnine was 0.083 mg/l in heart blood, 0.088 mg/l in peripheral blood and 4.0 mg/kg in gastric contents, respectively. Method validation was carried out in terms of linearity, accuracy, precision (intraday, interday) in blood. The assay is linear over 0.05~10 mg/l ($r^2$=0.999). Limit of detection (LOD) and limit of quantitation (LOQ) in blood were determined 0.02 mg/l (S/N=3) and 0.07 mg/l (S/N=10), respectively. Accuracy (bias%) of strychnine with 0.1, 1 and 10 mg/l was 12.0% (n=6), 9.3% (n=6) and 6.9% (n=6), respectively. Intraday precision (CV%) of strychnine with, 0.1, 1 and 10 mg/l were 6.4%, 10.4%, 1.2% (n=6), respectively. Interday precision (CV%) of strychnine with 0.1, 1 and 10 mg/l over three days were 24.0%, 18.5%, 13.8% (n=18), respectively. Relative recovery with 0.1, 1 and 10 mg/l (in blood) were 114.9%, 99.3% and 87.4% (n=6), respectively. The described method can be applied in forensic toxicology to determine strychnine in blood samples.

• Korean Journal of Food Science and Technology
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• v.51 no.4
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• pp.301-308
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• 2019

The antioxidant properties of Eriobotrya japonica leaf extract were investigated using DPPH and ABTS radical scavenging assay. The 80% ethanol extract of leaves ($IC_{50}$ values for DPPH and ABTS were 13.9 and $10.9{\mu}g/mL$, respectively) and young leaves ($IC_{50}$ values for DPPH and ABTS were 20.7 and $17.3{\mu}g/mL$, respectively) showed high radical scavenging activity. Additionally, the quantitative method for estimation of ellagic acid and chlorogenic acid from E. japonica leaves was optimized by HPLC/DAD. This method showed high linearity of the calibration curve with a coefficient of correlation ($R^2$) equal to 0.999. The LOD values for ellagic acid and chlorogenic acid were 2.35 and $0.73{\mu}g/mL$, respectively, whereas LOQ values were 7.13 and $2.22{\mu}g/mL$, respectively. Recovery of the two compounds was 99.7-108.0% with RSD values less than 5.31%. These results suggest that 80% ethanol extract of E. japonica leaves could serve as a potential source of natural antioxidant for us in various industrial applications.

• Environmental Analysis Health and Toxicology
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• v.18 no.2
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• pp.111-120
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• 2003

The validation of many synthetic chemicals that may pose a genetic hazard in our environment is of great concern at present. Since these substances are not limited to the original products, and enter the environment, they have become widespread environmental pollutants, thus leading to a variety of chemicals that possibly threaten the public health. In this respect, the regulation and evaluation of the chemical hazard playa very important role to environment and human health. The clastogenicity of 17 synthetic chemicals was evaluated in Chinese hamster lung fibroblast cells in vitro. 2-Nitroaniline (CAS No. 88-74-4) induced chromosomal aberrations with statistical significance at the concentration of 86.3 ${\mu}$g/ml in the absence of metabolic activation system. 1-Chloroanthraquinone (CAS No. 82-44-0) which is one of the most cytotoxic chemical among 17 chemicals tested revealed no clastogenicity in the range of 0.8 ∼ 3.0 ${\mu}$g/ml both in the presence and absence of S-9 metabolic activation system. From the results of chromosomal aberration assay with 17 synthetic chemicals in Chinese hamster lung cells in vitro, 2-Nitroaniline (CAS No. 88-74-4) revealed weak positive clastogenic results in this study.

• Proceedings of the ESK Conference
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• 1996.10a
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• pp.171-178
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• 1996

CFMS(Critical Function Monitoring System)는 원자력발전소의 비상시에 운전원에게 보조장보를 제공하는 지원시스템이다. 본 연구에서는 원자력발전소 울진 3&4호기 CFMS의 화면설계에 대한 인간 공학적 검토를 수행하였다. CFMS에 대한 규제 및 법규를 만족시키는 것과 CFMS 화면설계가 운전원에게 편의성을 제공할 수 있는지에 대한 인간공학적 타당성 평가의 사례를 제시하고자 한다. 본 연구에서는 인간공학적 검토의 공식적인 체계를 설정하기 위하여, CFMS 설계에서 필요한 인간공학 업무를 규정하고 수행절차를 기술하는 인간공학 프로그램 계획 (Human Factors Engineering Program Plan; HFEPP)과 설계평가의 방법과 업무 내용을 기술하는 확인 및 검증 프로그램 계획(Human Factors Engineerign Verification and Validation Plan; HFE V&V Plan)을 개발하였다. CFMS 설계에 대한 인간공학적 확인 및 검증을 위하여 CFMS의 정보 가용성 (information availability)과 화면 적합성 (display suitability)을 확인하였다. 정보 가용성의 확인은 CFMS 설계 요건서에서 정의된 정보를 중심으로 한 필요정보의 목록과 CFMS 화면상에서 제공되는 정보의 목록을 비교함으로써 수행되었다. 화면 적합성의 확인은 검토항목 선정, 검토양식 개발, 전문가 검토, 실험검토 등의 과정을 통하여 수행되었다. 관련 규제 문건으로 부터 규제요건상 만족해야할 최소한의 검토항목을 선정하고 검토양식을 개발하였으며, 인간공학 전문가들의 주관적 평가를 통하 여 수행되었다. 또한 화면의 조작방식에 대한 상세검토를 수행하였다. 검토결과로부터 발견된 문제점들은 HED (Human Engineerign Discrepance) 목록으로 정리하여 설계에 반영하도록 하였다.로 마음의 안정감, 몸의 긴장 이완에 따른 건강 상태 유지, 수업 집중도 향상 등이 나타났다. 위와 같은 종합 적 분석 결과에 따라, 본 연구는 제조 현장의 생산성 향상 및 품질 향상과 연계하여 작업자의 작업 집중도 향상, 작업자의 육체적, 심리적 변화에 따른 생산성 및 품질 향상 변화 정도 등의 산업공학(인간공학) 제 분야의 여러 측면에서 연구 및 적용이 가능하리라 사료된다.l, 시험군:25.90$\pm$7.16mg/d1, 47% 감소)를 나타내었으며, 시험군의 AUC는 대조군에 비해 39% 감소하였고, 혈중 아세트알데히드의 농도는 투여 60분후 시험군(3.96$\pm$0.07nmo1/$m\ell$)이 대조군(6.45$\pm$0,64nmo1/$m\ell$)에 비해 유의성 있는 감소(39%)를 나타내었으며, 시험군의 AUC는 대조군에 비해 48% 감소하였다 한편, 시험관내 에탄올 대사 효소에 대한 바이오짐의 효과를 검색해본 결과 바이오짐(2.0 $\mu\textrm{g}$/assay)에 의해 Aldehyde dehydrogenase(1.5unit/assay)의 활성이 14% 증가되었다. 본 연구의 결과로 볼 때, 비지니스 및 바이오짐은 음주 후 상승된 혈중 에탄을 농도 및 아세트알데히드의 농도를 현저히 감소시키는 효과가 있었다.량 보호 관리, 도시 소공원 개발, 역사 문화 공원 조성, 하천 공간 복원, 공원 시설 기능 개선, 이용 프로그램 개발, 공원 관리 개선, 환경 피해 녹지의 회복, 도시 환경 림 조성, 녹지 기능 증진, 도시 자연 경관 보전, 공원 녹지체계 구성, 공원 녹지 공급 균형, 주변 환경 녹화, 가로 녹화의 17개 시책을 제안하였다. 이러한 정책사업의 원활한 추진을 위해서는 기존의 관주도의 일방적인 공원 녹지 행정이 아닌 시민의 참여를 통

• Asian-Australasian Journal of Animal Sciences
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• v.26 no.10
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• pp.1474-1483
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• 2013

The objective was to evaluate the use of prediction equations based on the chemical composition of feedstuffs to estimate the values of apparent metabolisable energy corrected for nitrogen balance (AMEn) of corn and soybean meal for broilers. For performance and carcass characteristics, 1,200 one-d-old birds (male and female) were allotted to a completely randomised factorial $2{\times}8$ (two genders and eight experimental diets) with three replicates of each sex with 25 birds. In the metabolism trial, 240 eight-d-old birds were distributed in the same design, but with a split plot in time (age of evaluation) with five, four and three birds per plot, respectively, in stages 8 to 21, 22 to 35, and 36 to 42 d of age. The treatments consisted of the use of six equations systems to predict the AMEn content of feedstuffs, tables of food composition and AMEn values obtained by in vivo assay, totalling eight treatments. Means were compared by Scott-Knott test at 5% probability and a confidence interval of 95% was used to check the fit of the energy values of the diets to the requirements of the birds. As a result of this study, the use of prediction equations resulted in better adjustment to the broiler requirements, resulting in better performance and carcass characteristics compared to the use of tables, however, the use of energy values of feedstuffs obtained by in vivo assay is still the most effective. The best equations were: AMEn = 4,021.8-227.55 Ash (for corn) combined with AMEn = -822.33+69.54 CP-45.26 ADF+90.81 EE (for soybean meal); AMEn = 36.21 CP+85.44 EE+37.26 NFE (nitrogen-free extract) (for corn) combined with AMEn = 37.5 CP+46.39 EE+14.9 NFE (for soybean); and AMEn = 4,164.187+51.006 EE-197.663 Ash-35.689 CF-20.593 NDF (for corn and soybean meal).

• Journal of Food Hygiene and Safety
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• v.27 no.1
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• pp.37-41
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• 2012

The current standard for testing tetrodotoxin (TTX) in foodstuffs is the mouse bioassay (MBA) in Korea as in many other countries. However, this test suffers from potential ethical concerns over the use of live animals. In addition, the mouse bioassay does not test for a specific toxin thus a sample resulting in mouse incapacitation would need further confirmatory testing to determine the exact source toxin (e.g., TTX, STX, brevotoxin, etc.). Furthermore, though the time of death is proportional to toxicity in this assay, the dynamic range for this proportional relationship is small thus many samples must be diluted and new mice be injected to yield a result that falls within the quantitative dynamic range. Therefore, in recent years, there have been many efforts in this field to develop alternative assays. High performance liquid chromatography (HPLC) coupled with mass spectrometry (MS) has been emerged as one of the most promising options. A LC-MS-MS method involves solid-phase extraction (SPE) and followed by analysis using an electrospray in the positive ionization mode and multiple reactions monitoring (MRM). To adopt LC-MS-MS method as alternative standard for testing TTX, we performed a validation study for the quantification of TTX in puffer fish. This LC-MS-MS method showed good sensitivity as limits of detection (LOD) of $0.03{\sim}0.08{\mu}g/g$ and limits of quantification (LOQ) of $0.10{\sim}0.25{\mu}g/g$. The linearity ($r^2$) of tetrodotoxin were 0.9986~0.9997, the recovery were 80.9~103.0% and the relative standard deviations (RSD) were 4.3~13.0%. The correlation coefficient between the mouse bioassay and LC/MS/MS method was higher than 0.95.