• Journal of Pharmaceutical Investigation
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• v.38 no.6
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• pp.421-427
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• 2008

The purpose of the present study was to evaluate the bioequivalence of two etodolac capsules, Kuhnillodin capsule (Kuhnil. Co., Ltd., Seoul, Korea) as reference drug and Etodin capsule (Myungmun Pharm. Co., Ltd., Seoul, Korea) as test drug, according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty-three healthy male Korean volunteers received one capsule at the dose of 200 mg etodolac in a $2{\times}2$ crossover study. There was a one-week washout period between the doses. Plasma concentrations of etodolac were monitored by a high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) for over a period of 24 hr after the administration. $AUC_{0-24\;hr}$ was calculated by the linear trapezoidal rule method. $C_{max}$ and $T_{max}$ were compiled from the plasma concentration-time data. Analysis of variance (ANOVA) was carried out using logarithmically transformed $AUC_{0-24\;hr}$ and $C_{max}$. The 90% confidence intervals of the $AUC_{0-24\;hr}$ ratio and the $C_{max}$ ratio for Etodin/Kuhnillodin were $\log\;0.97{\sim}\log\;1.08$ and $\log\;0.89{\sim}\log\;1.19$, respectively. These values were within the acceptable bioequivalence intervals of $\log\;0.80{\sim}\log\;1.25$. Thus, our study demonstrated that Etodin was bioeqiovalent to Kuhnillodin preparation when the rate and extent of absorption between two preparations were compared.

• Journal of Ginseng Research
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• v.41 no.4
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• pp.540-547
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• 2017

Background: In general, after Panax ginseng is administered orally, intestinal microbes play a crucial role in its degradation and metabolization process. Studies on the metabolism of P. ginseng by microflora are important for obtaining a better understanding of their biological effects. Methods: In vitro biotransformation of P. ginseng extract by rat intestinal microflora was investigated at $37^{\circ}C$ for 24 h, and the simultaneous determination of the metabolites and metabolic profile of P. ginseng saponins by rat intestinal microflora was achieved using LC-MS/MS. Results: A total of seven ginsenosides were detected in the P. ginseng extract, including ginsenosides Rg1, Re, Rf, Rb1, Rc, Rb2, and Rd. In the transformed P. ginseng samples, considerable amounts of deglycosylated metabolite compound K and Rh1 were detected. In addition, minimal amounts of deglycosylated metabolites (ginsenosides Rg2, F1, F2, Rg3, and protopanaxatriol-type ginsenosides) and untransformed ginsenosides Re, Rg1, and Rd were detected at 24 h. The results indicated that the primary metabolites are compound K and Rh1, and the protopanaxadiol-type ginsenosides were more easily metabolized than protopanaxatriol-type ginsenosides. Conclusion: This is the first report of the identification and quantification of the metabolism and metabolic profile of P. ginseng extract in rat intestinal microflora using LC-MS/MS. The current study provided new insights for studying the metabolism and active metabolites of P. ginseng.

• Journal of Ginseng Research
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• v.42 no.3
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• pp.270-276
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• 2018

Background: Notoginsenoside Ft1 is a promising potential candidate for cardiovascular and cancer disease therapy owing to its positive pharmacological activities. However, the yield of Ft1 is ultralow utilizing reported methods. Herein, an acid hydrolyzing strategy was implemented in the acquirement of rare notoginsenoside Ft1. Methods: Chemical profiles were identified by ultraperformance liquid chromatography coupled with quadruple-time-of-flight and electrospray ionization mass spectrometry (UPLC-Q/TOF-ESI-MS). The acid hydrolyzing dynamic changes of chemical compositions and the possible transformation pathways of saponins were monitored by ultrahigh-performance LC coupled with tandem MS (UHPLC-MS/ MS). Results and conclusion: Notoginsenoside Ft1 was epimerized from notoginsenoside ST4, which was generated through cleaving the carbohydrate side chains at C-20 of notoginsenosides Fa and Fc, and vinaginsenoside R7, and further converted to other compounds via hydroxylation at C-25 or hydrolysis of the carbohydrate side chains at C-3 under the acid conditions. High temperature contributed to the hydroxylation reaction at C-25 and 25% acetic acid concentration was conducive to the preparation of notoginsenoside Ft1. C-20 epimers of notoginsenoside Ft1 and ST4 were successfully separated utilizing solvent method of acetic acid solution. The theoretical preparation yield rate of notoginsenoside Ft1 was about 1.8%, which would be beneficial to further study on its bioactivities and clinical application.

• Korean Journal of Food Science and Technology
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• v.35 no.4
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• pp.748-751
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• 2003

Acrylamide is considered as potential carcinogen and genotoxicant. Swedish National Food Administration reported that acrylamide was detected in heat treated starch rich food products. Acrylamide formation during food processing was confirmed by researchers of other countries including UK, Norway, Japan, Switzerland, and United States. It is noticed that the formation of acrylamide in potato products was greater than other food products. It may be due to high concentration of asparagine and glucose in potato products comparing to those of other food products. Interaction between asparagine and glucose during heat treatment resulted in acrylamide formation via Maillard reaction. Analytical method (LC-MS/MS) adopted by FDA was performed to monitor acrylamide concentrations in domestic food products. Acrylamide quantitation in several food categories, such as raw materials, boiled foods, fried foods, hardtacks, breads, breakfast cereals, potato chips, french fries, biscuits, and others, were carried out.

• Journal of Environmental Health Sciences
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• v.34 no.4
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• pp.271-278
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• 2008

Dialkylated phthalates have been commonly used as plasticizers and a variety of applications. Phthalate diesters have been shown to be developmental and reproductive toxicants. It is very difficult to exactly estimate the dose of dialkylated phthalates taken up by the general population because of environmental contamination. Urinary metabolites of phthalates enabled to estimate internal exposure. The objective of this study was quantitative determination of phthalate metabolites by LC/MS/MS with on-line cleanup method to analyze phthalate metabolites in Korean children's urine. We employed LC/MS/MS with on-line enrichment and column-switching techniques for this biological monitoring. Metabolites determined were 4 primary metabolites; MEHP, MnBP, MiBP, MEP and 2 secondary metabolites of DEHP; 5-OH-MEHP), 5-oxo-MEHP. We analyzed children's urine from 30 boys and 30 girls. The method detection limit of phthalate metabolites were 0.03 ng/mL for MEP, 1.05 ng/mL for MBP, 0.22 ng/mL for MEHP, 0.15 ng/mL for 5-OHMEHP and 0.16 ng/mL for 5-oxo-MEHP, respectively. Switching Column LC/MS/MS was proven to be a useful tool to determine metabolites of phthalate diesters in human urine. The correlation among phthalate metabolites was very high and statistically significant, except MEP. The children's age (months) was negatively correlated to the concentration of phthalate metabolites. The geometric mean concentration of phthalate metabolites (mg/g creatinine) in children's urine were 25.5 for MEP, 130.3 for MnBP, 56.8 for MiBP, 19.5 for MEHP, 85.6 for 5-OH-MEHP and 83.1 for 5-oxo-MEHP, respectively. Levels of estimated daily intake of parent phthalate compounds (${\mu}g$/kg bw/day) were 0.8 for DEP, 5.0 for DnBP, 1.9 for DiBP and $8.9{\sim}14.2$ for DEHP, respectively. Estimated daily intake for DEP and DiBP were lower than those of other studies but the value for DEHP was higher than that of other study.

• Journal of Pharmaceutical Investigation
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• v.37 no.6
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• pp.397-402
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• 2007

To evaluate the bioequivalence of two venlafaxine formulations, a standard 2-way randomized cross-over study was conducted in twenty-four healthy male Korean volunteers. A single oral dose of 75 mg of test formulation Venfaxine $OR^{(R)}$ (tablet) or reference formulation Efexor $XR^{(R)}$ (capsule) was administered with one-week washout period. Plasma concentrations of venlafaxine were assayed for over a period of 72 hours with a well validated method using liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS). The $mean{\pm}S.D$. of maximum concentration $(C_{max})$ and elimination half-life $(t_{1/2})$ were $64.7{\pm}28.5$ ng/mL, $9.2{\pm}3.0$ h, and $67.2{\pm}30.2$ ng/mL, $9.9{\pm}3.5$ h for test and reference formulations, respectively. Time to reach maximum concentration $(T_{max})$ expressed in median value (range), for the test and the reference, were 10 h (6-14) and 8h (4-12), respectively. Similarly, area under the plasma concentration-time curve, from time zero to last sampling time $(AUC_t)$ and from time zero to time infinity $(AUC_{inf})$, for test and reference formulations were $1185{\pm}755$, $1326{\pm}896$ and $1124{\pm}737$, $1185{\pm}755$ $ng{\cdot}h/mL$, respectively. The parametric 90% confidence intervals on the mean of the differences between the two formulations (test-reference) of the log transformed values of $AUC_t$, and $C_{max}$ were 0.9630 to 1.1383 and 0.8650 to 1.0446, respectively. The overall results indicate that the two formulations are bioequivalent and can be prescribe interchangeably.

• Korean Journal of Food Science and Technology
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• v.48 no.5
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• pp.405-412
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• 2016

Illegally adulterated compounds, such as impotency drugs and their synthetic analogues, which have been purported to enhance sexual potency or mood, have been constantly detected in foods including dietary supplements. The adulterated foods with these illegal compounds may threaten public health because their safety and efficacy have not been verified. This study was aimed at investigating illegal compounds in foods and counterfeit products. 54 illegal compounds were assayed using a simultaneous analytical method involving liquid chromatography equipped with photo diode array (LC-PDA) and LC coupled with tandem mass spectrometry (LC-MS/MS). The method was validated in terms of selectivity, linearity, limit of detection (LOD), limit of quantification (LOQ), precision and accuracy. In 48 of 161 samples, we identified 7 different illegal compounds, including sildenafil, tadalafil, chlropretadalafil, demethylsildenafil, dimethyl-thiosildenafil, icariin and yohimbine. When purchasing products marketed for erectile dysfunction or aphrodisiacs, ulmost care should be taken owing to the possible presence of these illegal compounds.

• Korean Journal of Food Science and Technology
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• v.48 no.5
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• pp.424-429
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• 2016

Globally, obesity has been recognized as a serious health problem. Recently, slimming foods for weight loss and maintenance were found to contain anti-obesity drugs, their analogues, and prohibited ingredients. To avoid inspections by the Government, structurally modified analogs have been continuously synthesized. For rapid determination of adulterated slimming products, we simultaneously analyzed 21 illegal compounds using liquid chromatography (LC) equipped with photo diode array, and LC coupled with tandem mass spectrometry. The validation of the method was performed with regard to selectivity, linearity, limit of detection, limit of quantification, precision, and accuracy. We purchased 128 samples from the Korean market and online sources in the year 2015. In 31 samples, 3 illegal compounds were detected as follows: 9.9-135.3 mg/g of sibutramine, 0.2-17.5 mg/g of yohimbine, and 1.8 mg/g of icariin. This simultaneous detection method might prove to be a simple and rapid analysis for monitoring illegal compounds in slimming foods.

• Korean Journal of Food Science and Technology
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• v.51 no.1
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• pp.90-96
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• 2019

Unripe astringent persimmon (Diospyros kaki Thunb. cv. Cheongdo-Bansi) is a by-product produced when thinning out the superfluous fruit of persimmon. We investigated whether unripe astringent persimmon has antioxidative and anti-inflammatory effects. Unripe astringent persimmon extract was fractionated sequentially in n-hexane, chloroform, ethyl acetate, n-butanol, and water. The ethyl acetate fraction had the highest total phenolic content, total flavonoid content, and antioxidant capacity compared to those of the other fractions. Pretreatment of lipopolysaccharide-stimulated RAW 264.7 macrophages with the ethyl acetate fraction reduced nitric oxide, interleukin-6, and intracellular oxidative stress in a dose-dependent manner. Ultra-high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry analysis revealed gallic acid, protocatechuic acid, 4-hydroxybenzoic acid, quercetin-3-O-glucoside, quercetin, and p-coumaric acid as the phenolic compounds of the ethyl acetate fraction. Collectively, these findings suggest that unripe astringent persimmon is a source of functional materials that can promote antioxidative and anti-inflammatory effects.

• Korean Journal of Environmental Agriculture
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• v.39 no.4
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• pp.375-383
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• 2020

BACKGROUND: Bisphenol A (BPA) is a chemical widely used in polycarbonate plastics, epoxy resins. BPA is an endocrine disruptor. Residue of BPA in agricultural environments is a major concern. The objective of this study was to understand the characteristics of the uptake and distribution of BPA and its metabolites introduced into the agricultural environment to crops, and to use it as basic data for further research on reduction of BPA in agricultural products. METHODS AND RESULTS: This study established the analysis method of BPA and its metabolites in soil and crops, and estimated the intake of BPA and its metabolites from lettuce (Lactuca sativa) grown in sandy loam and loam soil, which are representative soils in Korea. The two major metabolites of BPA were 4-hydroxyacetophenone (4-HAP) and 4-hydroxybenzoic acid (4-HBA). BPA, 4-HAP and 4-HBA have been analyzed by using liquid chromatography tandem mass spectrometry (LC-MS/MS). These substances were detected in sandy loam and loam soil, indicating that certain portions of BPA were converted to 4-HAP and 4-HBA in the soil; however, it was observed that only 4-HBA migrated to lettuce through the roots into crops. CONCLUSION: The uptake residues showed the BPA and 4-HAP were not detected in lettuces grown on sandy loam (SL) and loam (L) soil treatments that were applied with of 10 ng/g, 50 ng/kg and 500 ng/g of BPA. However, the 4-HBA was detected at the level of 7 ng/g and 11 ng/g in the lettuce grown in sandy loam and loam soil that were treated with the 500 ng/g of BPA, respectively, while the 8 ng/g of 4-HBA was measured in the lettuce cultivated in the loam that was treated with 100 ng/g of BPA. This result presents that the BPA persisting in the soil of the pot was absorbed through the lettuce roots and then distributed in the lettuce leaves at the converted form of 4-HBA, what is the oxidative metabolite of BPA.