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Bioequivalence of pioglitazone tablet to Actos® tablet (Pioglitazone 30 mg) (액토스정®(피오글리타존 30 mg)에 대한 염산피오글리타존정의 생물학적동등성)

  • Yeom, Hyesun;Lee, Tae Ho;Youm, Jeong-Rok;Song, Jin-Ho;Han, Sang Beom
    • Analytical Science and Technology
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    • v.22 no.1
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    • pp.101-108
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    • 2009
  • The bioequivalence of two pioglitazone tablets, Actos$^{(R)}$ tablet (Takeda Chemical Industries, reference drug) and Pioglitazone tablet (Boryung Company, test drug) was evaluated according to the guidelines of Korea Food and Drug Administration. Twenty-eight healthy male Korean volunteers received each medicine (pioglitazone dose of 30 mg) in a $2{\times}2$ crossover study with one week washout interval. After drug administration, blood samples were collected at specific time intervals from 0-36 hours. The plasma concentrations of pioglitazone were determined by high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). The total chromatographic run time was 5 min and calibration curves were linear over the concentration range of 5-2000 ng/mL for pioglitazone. The method was validated for selectivity, sensitivity, linearity, accuracy and precision. The pharmacokinetic parameters were determined from the plasma concentration-time profiles of both formulations. The primary calculated pharmacokinetic parameters were compared statistically to evaluate bioequivalence between the two preparations. The 90% confidence intervals of the $AUC_t$ ratio and the $C_{max}$ ratio for Pioglitazone tablet and Actos$^{(R)}$ tablet were log0.9422~log1.1040 and log0.9200~log1.1556, respectively. Based on the statistical considerations, we can conclude that the test drug, Pioglitazone tablet was bioequivalent to the reference drug, Actos$^{(R)}$ tablet.

The measurement of dicamba in soil and plants (토양 및 식물 중 디캄바 측정법에 대한 연구)

  • Shin, Ho-Sang
    • Analytical Science and Technology
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    • v.22 no.6
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    • pp.480-487
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    • 2009
  • The herbicide dicamba (2-methoxy-3,6-dichlorobenzoic acid) in soil and plants was determined by gas chromatography-mass spectrometry (GC/MS). The samples were extracted with diethyl ether at pH 2, and washed with 0.1 N HCl, and then dried. The dried residue was derivatized in 1 mL of 10% $H_2SO_4$-MeOH for 2 hr at $80^{\circ}C$. The reaction mixture was neutralized with 4 mL of sodium bicarbonate solution and reextracted with 5 mL of diethyl ether. After the extract was concentrated, dicamba was determined by GC/MS-SIM mode. There was good linearity above 0.999 in the ranges of the $1.0{\sim}100{\mu}g/kg$. Total 42 sample including 32 soil samples and 10 plants samples were analyzed by developed method. Dicamba was detected in the concentration range of $2.9-123.9{\mu}g/kg$ in 15 samples among 32 soil samples and in the concentration range of $43-33,252{\mu}g/kg$ in 5 samples among 10 plants samples. A cause of the wither and die of the pine trees is suspected to spray dicamba around or directly to them.

Determination of volatile and residual iodine during the dissolution of spent nuclear fuel (사용 후 핵연료 용해 중 휘발 및 잔류 요오드 분석)

  • Kim, Jung Suk;Park, Soon Dal;Jeon, Young Shin;Ha, Young Keong;Song, Kyuseok
    • Analytical Science and Technology
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    • v.22 no.5
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    • pp.395-406
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    • 2009
  • The determination of iodine in the spent nuclear fuel and the volatile behavior during its acid dissolution have been studied by NAA(neutron activation analysis) and electron probe microanalysis (EPMA). Simulated spent fuels (SIMFUELs) were dissolved in $HNO_3$(1+1) at $90^{\circ}C$ for 8 hours. The iodine remained in a dissolver solution after dissolution, and that condensed in dissolution apparatus and trapped in the adsorbent by volatilization during the dissolution were determined, respectively. The condensed iodine was recovered by the redistillation with $HNO_3$(1+1) after transfer of the dissolver solution. The iodines in the dissolver and redistilled solution were separated by solvent extraction followed by ion exchange or precipitation method and determined by RNAA (radiochemical neutron activation analysis). The ion exchange column and filtration kit used for the isolation of iodine, which were prepared with a polyethylene tube, were used as an insert in the pneumatic tube for neutron irradiation. The iodine volatilized during the dissolution of SIMFUELs was collected in a trapping tube containing Ag-silica gel (Ag-impregnated silica gel) adsorbent, and the distribution of iodine trapped in the adsorbents were determined by EPMA. The adsorbing characteristics shown with the SIMFUELs were compared with those shown with a real spent fuel from the nuclear power plant.

Analysis of clenbuterol in bovine muscle and milk by LC-ESI/MS/MS (LC-ESI/MS/MS를 이용한 소고기와 우유에서의 클렌부테롤 분석)

  • Hong, Selyung;Jeong, Jiyoon;Park, Hyejin;Lee, Soonho;Lee, Jongok
    • Analytical Science and Technology
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    • v.21 no.6
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    • pp.535-542
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    • 2008
  • A liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI/MS/MS) method was developed for the determination and confirmation of clenbuterol in bovine muscle and milk. Clenbuterol and clenbuterol-D9 using as an internal standard in samples were extracted with ethyl acetate after hydrolysis and evaporated to dryness. The extracts were dissolved in 20% methanol and cleaned using HLB solid-phase extraction cartridge. The analytes were detected by LC-ESI/MS/MS on a $C_{18}$ column. Mass spectral acquisition was done in selected reaction monitoring (SRM) in positive ion mode to provide a high degree of sensitivity. Using MS/MS with SRM mode, the transitions (precursor to product) monitored were m/z 277${\rightarrow}$203 for clenbuterol, and m/z 286${\rightarrow}$204 for internal standard. The limits of quantitation (LOQ) and mean recoveries of clenbuterol in bovine muscle were $0.2{\mu}g/kg$ and 84.3~91.1%, respectively. The LOQ and mean recoveries in milk were $0.05{\mu}g/kg$ and 87.7~98.3%, respectively.

Study on stability test of in process sample of recombinant Protein A (재조합 단백질 A 제조공정시료의 안정성실험에 관한 연구)

  • Kim, Yoo Gon;Lee, Woo Jong;Won, Chan Hee;Shin, Chul Soo
    • Analytical Science and Technology
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    • v.25 no.6
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    • pp.483-491
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    • 2012
  • This study is to investigate the issues on how to secure stability during the purification process for the production of recombinant protein A. The final recombinant protein A is produced by passing through the cation exchange column (SP) and the anion-exchange column (Q) during the production process, for which the samples produced by the step-by-step processes can be exposed to trouble in securing stable storage in case the next process cannot be taken within the proper time period. Accordingly, this study aims to evaluate the proper storage conditions and length of time when storing samples produced in the production process. That is, in this study, how to store fair samples, how long the storage period should be set up, and how to evaluate the security of its quality depending on time are dealt with. The items to be experimented with were enodotoxin, SDS-PAGE, HPLC purity and concentration. Experimental results showed that after passing the cation exchange column, when stored at $4^{\circ}C$ or room temperature, SDS-PAGE showed a major band, endotoxin is 5.0 Eu/mg or less, and concentration is on average of 8.21 to 8.24 mg/mL and RSD% 0.10~0.62%. In addition, HLPC purity showed somewhat stable results; at the HPLC purity 214 nm, the average is 99.24% to 99.37% and RSD% is 0.22~0.29%, while the average is 89.72% to 89.80% and RSD% 0.62~1.26% at 280 nm. On the contrary, after passing the anion exchange column, when stored at $4^{\circ}C$ or room temperature, SDS-PAGE revealed the major band, endotoxin is 0.5 Eu/mg or less, and concentration is on average of 5.59 mg/mL and RSD% 0.03~0.10%. when it comes to HLPC purity, the result showed that at the HPLC purity 214 nm, the average is 99.74% and RSD% is 0.10~0.11%, while the average is 96.16% to 96.85% and RSD% 0.72~1.13%. In conclusion, the stability of fair samples of recombinant protein A during the manufacturing process could be obtained without substance decomposition for 7~8 days at $4^{\circ}C$ or 20~21 days at room temperature.

Determination of metabolites of prostanozol in human urine by LC/ESI/MS and GC/TOF-MS (LC/ESI/MS와 GC/TOF-MS를 이용한 인체뇨시료에서의 Prostanozol 대사체 검출)

  • Yum, Tae-Woo;Paeng, Ki-Jung;Kim, Yun-Je
    • Analytical Science and Technology
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    • v.24 no.3
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    • pp.173-182
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    • 2011
  • This research examined prostanozol and its metabolites in urine of women who took the medicine (prostanozol). Prostanozol and its metabolites were successfully separated and detected by using LC/ESI/MS and GC/TOF-MS. Mass spectrum of LC/ESI/MS estimated molecular weight of Prostanozol and its metabolites and that of GC/TOF-MS verified them. For M1, carbon number 17 of Prostanozol substituted to a keto group and it is called 17-keto-Prostanozol. M2 turned out to be hydroxy-17-keto-Prostanozol. It came from substitution of one hydroxyl group of pyrazole nucleus and A-ring of M1. Substitution of one hydroxyl group of B-ring or C-ring became M3, hydroxy-17-keto-Prostanozol. M4 was found to be a hydroxy-17-keto-Prostsnozol transposed from one hydroxyl group to a D-ring. M5 has a hydroxyl group of carbon number 17. One hydroxyl group is substituted from B-ring or C-ring and it is assumed to be hydroxy-17-hydroxy-Prostanozol. M6 was turned out to be dihydroxy-17-keto-Prostanozol transposed from one hydroxyl group to pyrazole nucleus or A-ring and to B-ring or C-ring. Like M6, M7 has a keto group at carbon number 17 and was identified as dihydroxy-17-keto-Prostanozol. M7 has one hydroxyl group at pyrazole nucleus or A-ring and also at D-ring. At last M8 was found to be dihydroxy-17-hydroxy-Prostanozol. Pyrazole nucleus or A-ring has got one hydroxyl group and other rings were substituted to another hydroxyl group. From above, M5, M7 and M8 were verified as new metabolites that were not discovered yet. Prostanozol and all of the 8 metabolites formed glucuronic conjugates as a result of conjugation reaction test in human body. Some of 8 metabolites were excreted without forming conjugates. Particularly M6 and M7 were excreted as sulfate conjugates.

Effects of Fermented Red Ginseng Supplementation on Blood Glucose and Insulin Resistance in Type 2 Diabetic Patients (발효홍삼이 제2형 당뇨병 환자의 혈당 및 인슐린저항성에 미치는 영향)

  • Kim, Hey-Ok;Park, Min-Jung;Han, Ji-Sook
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.40 no.5
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    • pp.696-703
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    • 2011
  • We performed a randomized placebo-controlled trial to determine whether or not fermented red ginseng supplementation modulates blood glucose and insulin resistance in type 2 diabetic patients. A total of 38 patients were randomized to either a fermented red ginseng group or placebo group. The patients in the experimental or placebo group consumed 780 mg of fermented red ginseng or cellulose supplement per day for 12 weeks, respectively. Lifestyle factors and dietary intakes of the patients were not altered during the 12-weeks period. In the fermented red ginseng group after 12 weeks, the fasting blood glucose levels were significantly decreased ($136.29{\pm}16.45$ mg/dL to $127.71{\pm}17.74$ mg/dL) and $HbA_1c$ was also decreased. Especially, high HbA1c (HbA1c $\geq$8%, $8.45{\pm}0.56%$ to $7.82{\pm}0.53%$) was significantly decreased compared to low HbA1c (HbA1c <8%, $6.71{\pm}0.85%$ to $6.44{\pm}0.49%$) in the fermented red ginseng group. Serum low-density lipoprotein was slightly decreased in the fermented red ginseng group compared to the placebo group. Homeostasis model assessment-insulin resistance was significantly reduced in the fermented red ginseng group compared to the placebo group. These results suggest that fermented red ginseng supplementation could be helpful to reduce blood glucose by improving insulin resistance in type 2 diabetic patients.

Effect of Fermented Yacon (Smallanthus Sonchifolius) Leaves Tea on Blood Glucose Levels and Glucose Metabolism in High-Fat Diet and Streptozotocin-Induced Type 2 Diabetic Mice (야콘잎 발효차가 고지방식이와 스트렙토조토신으로 유도한 제2형 당뇨마우스의 혈당 및 당대사에 미치는 영향)

  • Kim, In-Sook;Lee, Jin;Lee, Jeom-Sook;Shin, Dong-Young;Kim, Myung-Joo;Lee, Mi-Kyung
    • Journal of Nutrition and Health
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    • v.43 no.4
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    • pp.333-341
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    • 2010
  • The aim of this study was to investigate the hypolgycemic activity of water extract of fermented yacon (Smallanthus sonchifolius) leaves tea (Yacon LWE) in high-fat diet (HFD)/streptozotocin (STZ)-induced diabetic mice. Male ICR mice were fed with a HFD (37% calories from fat) for 4 weeks prior to intraperitoneal injection with STZ (100 mg/kg body weight). Diabetic mice were supplemented with two doses of Yacon LWE (0.16% and 0.8%, wt/wt) for 6 weeks. The supplementation of high-dose Yacon LWE significantly lowered blood glucose levels and plasma ALT and AST activities compared with the control group. High-dose Yacon LWE also improved the insulin tolerance without any changes in plasma and pancreatic insulin concentrations in HFD/STZ-induced diabetic mice. Yacon LWE supplementation increased the insulin staining of pancreatic $\beta$-cells in a dose-dependent manner. Both 0.16% and 0.8% of Yacon LWE significantly elevated plasma leptin concentration, hepatic glucokinase activity and glucokinase/glucose-6-phosphatase ratio compared with the control group. However, glycosylated hemoglobin concentration was not different among the groups. These results suggest that high-dose Yacon LWE lowers the blood glucose level partly by enhancing insulin sensitivity and hepatic glucose metabolism in type 2 diabetic mice.

Comparison in Serum Constituents of Cultured Marine Fishes in Early Summer Season (주요 양식어류의 하절기 혈액성분 비교)

  • 전중균;김형배
    • Journal of Aquaculture
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    • v.11 no.4
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    • pp.547-556
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    • 1998
  • This study was performed to obtain the basic data on the serum constituents of several marine fish spesies commonly cultured in Korea. Blood samples taken from six species of fish were analyzed for various components of serum, total protein (TP), albumin (ALB), triglyceride (TRIG), cholesterol (CHOL), glucose (GLC), lipase (LIPA), amylase (AMYL), aspartate transaminoferase (AST), sodium (Na), potassium (K), chloride (CI) and phosphorus (PHOS). The fish used were coho salmon (Oncorhynchus kisutch), rock fish (Sebastes schlegeli), sea bass (Lateolabrax japonicus), olive flounder (Paralichthys olivaceus), rock fish (Sebastes schlegeli), sea bass (Lateolabrax japonicus), olive flounder (Paralichthys olivaceus), parrot fish (Oplegnathus fasciatus) and jack mackerel (Trachurus jaonicus) reared at the Chungmu Experimental Fish Culture Station of KORDI when the water tempetature was ca. 16.5$^{\circ}C$. There were significant differences in TRIG, CHOL, LIPA and AMYZ among the species analyzed. TRIG concentratin were ranged 178~180mg/dl in jack mackeerel and rock fish, 126~159 mg/dl in olive flounder and sea bass, and 102~114 mg/dl in coho salmon and parrot fish, respectively. Jack mackerel showed the highest levels in CHOL (255mg/dl) and GLC(138mg/dl) among species. LIPA levels were recorded 256 U/dl in coho salmon, 41~42 U/dl in parrot fish and rock fisk, and 5~11 U/dl jack mackerel and sea bass, respectively. AMYL activity of coho salmon was measured as 2, 665 U/dl, and that of jack mackerel was 1,210 U/dl while sea bass showed 60 U/dl and parrot fish, olive flounder and rock fish had at most 5 U/dl. On the other hand, there was no significant difference in the concentration of Na and CI. Na and K were proved that they were negatively correlated in all the species. Generally, among blood components, PHOS and CHOL levels were different depending on environmental temperature of each fish species, especially in olive flounder. Rock fish and parrot fish showed high blood concentration of those components during low temperature period while olive flounder and jack mackerel reached high level during their optimal environmental temperature period. The electrolyte concentration and LIPA activity were high during low water temperature period, in general, but TP and ALB concentrations were high during optimal temperature period. The concentrations of TRIG, CHOL and GLC, those which were used as energy sourses, were different among species by season.

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Effect of Black Garlic and Herb Formulas on Lipid Profiles and Antioxidant Status in Rats by Interval Running Training (간헐적 운동부하에서 흑마늘과 생약재의 복합처방이 흰쥐의 체내 지질 성분 및 항산화에 미치는 영향)

  • Lee, Soo Jung;Kim, In Sung;Lee, Hye Jin;Oh, Soo Jeong;Shin, Jung Hye;Kim, Jeong Gyun;Sung, Nak Ju
    • Journal of Life Science
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    • v.23 no.12
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    • pp.1436-1444
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    • 2013
  • To improve the functionality of black garlic drinks, black garlic extract (5%) and five herb extracts (1%) were mixed in 70:30 (v/v) ratios as BHF1, and BHF2 was prepared using a 3X concentration of BHF1. After the black garlic and herb formulas (BHFs) were administered over the course of five weeks in rats by interval running training, the lipid profiles and the antioxidant enzyme activities were tested. The total phenolic content of the BHFs were significantly higher in BHF2 than they were in BHF1, and their antioxidant activities were dependent upon the total phenolic content. No significant difference was found in the total serum protein levels among the rats in the Ex-con group by interval running training and the rats in the BHFs-fed groups. However, the albumin level was significantly higher in the Ex-BHF2 to Ex-con group. AST and ALT activities significantly decreased in the BHFs-fed groups compared to the Ex-con group. In terms of changes in the serum lipid profiles, no significant difference was found between the specimens that underwent interval running training and those that did not undergo interval running training. Triglyceride levels, total cholesterol, LDL-C, and HTR levels in the serum were significantly decreased in the Ex-BHF2 to Ex-con group. No significant difference was found in the total lipid levels in the livers of the BHFs-fed groups and the Ex-con group. The triglyceride levels and total cholesterol levels in the Ex-BHF2 group were significantly lower compared to another group. Hepatic catalase activity was significantly increased in the Ex-BHF2 group, but SOD and GSH-px activities were significantly increased as the concentration of the BHF. The antioxidant enzyme activities by supplementation of BHFs increased; thus, three intakes of BHF each day could improve antioxidant status against different types of oxidative stress.