• 제목/요약/키워드: Rat plasma

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Determination of a Novel Antiangiogenic Agent KR-31831 in Rat Plasma by Liquid Chromatography-Tandem Mass Spectrometry

  • Kim, Sook-Jin;Lee, Seung-Seok;Ji, Hye-Young;Lee, Hong-Il;Lee, Seon-Kyoung;Yi, Kyu-Yang;Yoo, Seong-Eun;Hwang, Jeong-Sook;Lee, Hye-Suk
    • Proceedings of the PSK Conference
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    • 2003.10b
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    • pp.217.2-217.2
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    • 2003
  • A liquid chromatography-tandem mass spectrometric (LC/MS/MS) method was developed for the determination of a new anti-angiogenic drug KR-31831 in rat plasma. KR-31831 and internal standard, KR-31543 were extracted from rat plasma with dichloromethane at basic pH. A reverse-phase LC separation was performed on Luna C8 column with the mixture of acetonitrile-ammonium formate (10 mM, pH 4.5) (67:33, v/v) as mobile phase. The detection of analytes was performed using an electrospray ionization tandem mass spectrometry in the multiple-reaction-monitoring mode. (omitted)

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Effects of cheungho aqua-acupunctureat gansoo$(BL_{18})$ and illweul$(GB_{14})$ on plasma lipid composition in rat fed high fat diet (간유(肝兪) 및 일월(日月) 청호약침(靑蒿藥鍼)이 고지방(高脂肪) 급여(給與) 흰쥐의 혈청(血淸) 지질구성(脂質構成)에 미치는 영향(影響))

  • Lee Joon-Moo
    • Korean Journal of Acupuncture
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    • v.20 no.3
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    • pp.91-99
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    • 2003
  • Effects of cheungho aqua-acupuncture at gansoo$(BL_{18})$ and illweul$(GB_{14})$ on plasma lipid composition were investigated in rat fed high fat diet. Body weight gain showed a tendency to decrease in aqua-acupuncture groups and in aqua-acupuncture groups, gansoo and illweul join aqua-acupuncture group showed a lower values than other aqua-acupuncture groups. Concentrations of plasma triglyceride, free fatty acids, lipoprotein and glucose showed a tendency to decreasea in the aqua-acupuncture groups. However in aqua-acupuncture groups, these values showed no significantly different. In plasma lipid composition, total cholesterol and LDL- cholesterol showed a tendency to decrease in aqua-acupuncture groups, however the values of LDL-cholesterol showed no significantly different in the aqua-acupuncture groups. HDL-cholesterol concentration showed a tendency to increase in aqua-acupuncture groups and in aqua-acupuncture groups, gansoo aqua-acupuncture group showed a high value.

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Metabolic and pharmacokinetic profiles of sulfamethazine in the rat (Rat에서 설파메타진의 대사 및 약물동태학)

  • Yun, Hyo-in;Park, Seung-chun;Park, Jong-myung;Cho, Joon-hyoung;Lee, Mun-han
    • Korean Journal of Veterinary Research
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    • v.35 no.4
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    • pp.691-698
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    • 1995
  • We used rats as the experimental animal for the elucidation of metabolic patterns and pharmacokinetic profiles of SMZ in the rat, by use of the urine and plasma from predetermined intervals, respectively. Information herefrom would give some insight into species differences and sex differences in the metabolism and pharamcokinetics of drugs, at least SMZ in particular. Results would be summarized as follows: 1. There were two hydorxy metabolites(5-hydroxysulfamethazine and 6-hydroxyethylsulfamethazine) and an acetyl derivative($N_4$-acetyl sulfamethazine) in the 24h-collected urine, on confirmation with each standard materials. There were also two unknown metabolites therein. 2. In the viewpoint of quantitative aspect, $N_4$-acetylsulfamethazine was the largest, hence it is assumed that the acetyl pathway is the major one in the metabolism of SMZ in the rat. 3. As regards sex difference in the rat, the male had more metabolic capacity than the female in metabolism of SMZ. 4. The concenteration-time curves of sulfamethazine(20mg/kg, po) in the plasma compartment were fitted to a one-compartment open model by use of a computer program(NONLIN). 5. There were significant differences(P<0.05) in the pharmacokinetics of sulfamethazine between two sexes in the rat, with higher disposition rate in the male. 6. The emergence of $N_4AcSMZ$ metabolized from SMZ was fast in the plasma of the rat. Half-life of $N_4AcSMZ$ was also. significantly different(P<0.05) between two sexes, suggesting differences in the eliminatory capacity of $N_4AcSMZ$.

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Comparison of rosiglitazone metabolite profiles in rat plasma between intraperitoneal and oral administration and identifcation of a novel metabolite by liquid chromatography-triple time of flight mass spectrometry (액체크로마토그라피-삼중비행시간질량분석기를 사용한 rosiglitazone의 복강 및 경구투여 후 대사체 비교 분석)

  • Park, Minho;Na, Sook-Hee;Lee, Hee-Joo;Shin, Byung-Hee;An, Byung-Jun;Shin, Young G.
    • Analytical Science and Technology
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    • v.28 no.2
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    • pp.132-138
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    • 2015
  • Rosiglitazone metabolites in rat plasma were analyzed after intraperitoneal and oral administration to rats. Seven metabolites (M1-M7) were detected in rat plasma (IP and PO), and the structures were confirmed using liquid chromatography-triple time of flight (TOF) mass spectrometry; as a result, the most abundant metabolite was M5, a de-methylated rosiglitazone. Other minor in vivo metabolites were driven from monooxygenation and demethylation (M2), thiazolidinedione ring-opening (M1, M3), mono-oxygenation (M4, M7), and mono-oxygenation followed by sulfation (M6). Among them, M1 was found to be a 3-{p-[2-(N-methyl-N-2-pyridylamino)ethoxy]phenyl}-2-(methylsulfinyl)propionamide, which is a novel metabolite of rosiglitazone. There was no significant difference in the metabolic profiles resulting from the two administrations. The findings of this study provide the first comparison of circulating metabolite profiles of rosiglitazone in rat after IP and PO administration and a novel metabolite of rosiglitazone in rat plasma.

Development and Validation of a Liquid Chromatography-Tandem Mass Spectrometry Method for the Determination of ε-Acetamidocaproic Acid in Rat Plasma

  • Kim, Tae Hyun;Choi, Yong Seok;Choi, Young Hee;Kim, Yoon Gyoon
    • Toxicological Research
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    • v.29 no.3
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    • pp.203-209
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    • 2013
  • A simple and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of ${\varepsilon}$-acetamidocaproic acid (AACA), the primary metabolite of zinc acexamate (ZAC), in rat plasma by using normetanephrine as an internal standard. Sample preparation involved protein precipitation using methanol. Separation was achieved on a Gemini-NX $C_{18}$ column ($150mm{\times}2.0mm$, i.d., 3 ${\mu}m$ particle size) using a mixture of 0.1% formic acid-water : acetonitrile (80 : 20, v/v) as the mobile phase at a flow rate of 200 ${\mu}l/min$. Quantification was performed on a triple quadrupole mass spectrometer employing electrospray ionization and operating in multiple reaction monitoring (MRM) and positive ion mode. The total chromatographic run time was 4.0 min, and the calibration curves of AACA were linear over the concentration range of 20~5000 ng/ml in rat plasma. The coefficient of variation and relative error at four QC levels were ranged from 1.0% to 5.8% and from -8.4% to 6.6%, respectively. The present method was successfully applied for estimating the pharmacokinetic parameters of AACA following intravenous or oral administration of ZAC to rats.

A Simple and Efficient Method to Determine Montelukast in Rat Plasma Using Liquid-Liquid Extraction and Tandem Mass Spectrometry

  • Kim, Dong Yoon;Lee, Hyo Chun;Jang, Yong Jin;Kim, Jin Hee;Lee, Ha Ryeong;Kang, Myung Joo;Choi, Yong Seok
    • Mass Spectrometry Letters
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    • v.11 no.4
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    • pp.71-76
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    • 2020
  • While montelukast (ML), a cysteinyl-leukotriene type 1 receptor (CysLT1) antagonist is widely used to treat symptoms of rhinitis or asthma, its formulations are mainly limited to solid preparation due to its instability. Recently, there have been attempts to develop various ML dosage forms, and this situation increases the demand of sensitive and creditable methods to determine ML in various samples such as plasma. Thus, here, a simple and efficient method to determine ML in rat plasma using liquid-liquid extraction (LLE) and multiple reaction monitoring was presented. The mixture of DCM:EtOAc (25:75, v/v), the optimized extract solvent for LLE was found to be effective to extract ML without hydrophilic salts and proteins from the sample with limited volume. Also, the use of zafirlukast, instead of expensive ML-d6, as the internal standard makes the present method economical. The developed method was successfully validated in terms of selectivity, matrix effects (-14.8--6.9%), linearity (r230.998 within 0.5-500 ng/mL), sensitivity (the limit of detection and the lower limit of quantitation, ≤0.5 ng/mL), accuracy (88.4-100.6%), precision (3.0-13.3%), and recovery (80.8-86.3%) by following the FDA guidelines. Finally, the applicability of the validated method to pharmacokinetics (PK) studies was confirmed by the successful determination of PK parameters through it following oral administration of Singulair® granule in rats. Therefore, the present method can contribute to the development of new ML formulations through its performance to determine ML in rat plasma efficiently and sensitively.

FABRICATION OF PLATELET-RICH PLASMA IN A RAT MODEL AND THE EFFICACY TEST IN VITRO (백서에서 혈소판 풍부 혈장의 제작과 유효성에 대한 실험적 연구)

  • Lee, Sang-Hoon;Cho, Young-Uk;Chi, Hyun-Sook;Ahn, Kang-Min;Lee, Bu-Kyu
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.29 no.2
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    • pp.113-122
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    • 2007
  • Purpose: Platelet-rich plasma (PRP) is known to accelerate and/or enhance hard and soft tissue healing and regeneration. As such, PRP has been used in various clinical fields of surgery. Recently there have been several attempts to use PRP in the field of tissue engineering. However, some controversies still exist on exact mechanism and benefits of PRP. Therefore various animal experiments are necessary to reveal the effect of the PRP. However, even if animal experiment is performed, the efficacy of the experiment could not be validated due to absence of an animal PRP model. The purpose of this study is to establish rat PRP model by comparing several PRP fabricating methods, and to assay growth factor concentration in the PRP. Materials and methods: Rat blood samples were collected from nine SD rat (body weight: 600-800g). PRP was prepared using three different PRP fabricating methods according to previously reported literatures. (Method 1: 800 rpm, 15 minute, single centrifuge; Method 2: 1000 rpm, 10 minute, double centrifuge; Method 3: 3000 rpm, 4min and 2500 rpm, 8 min, double centrifuge). Platelet counts were evaluated in an automated machine before and after PRP fabrications. In terms of growth factor assay, prepared PRP were activated with 100 unit thrombin and 10% calcium chloride. Growth factor (PDGF-BB, VEGF) concentrations on incubation time were determined by sandwich-ELISA technique. Results: An average of 3ml (via infraorbital venous plexus) to 15ml (via celiac axis) the rat blood could be collected. By using Method 3 (3000 rpm, 4 min and 2500 rpm, 8 min, double centrifugation), around 1.5ml of PRP could be prepared. This method allowed us to concentrate platelet 3.77-fold on average. PDGF-BB concentration (mean, 1942.10 pg/ml after 1 hour incubation) and VEGF concentration (mean, 952.71 pg/ml after 1 hour incubation) in activated PRP were higher than those in untreated blood. Also PDGF-BB showed constant concentration during 4-hour incubation, while VEGF concentration was decreased after 1 hour. Conclusion: Total 11,000 g minute separation and condensation double centrifuge method can produce efficient platelet-rich plasma. Platelet-rich plasma activated with thrombin has showed higher concentrations of growth factors such as PDGF-BB and VEGF, compared to the control group. Platelet-rich plasma model in a rat model was confirmed in this study.

Effect of Ojayeonjonghwan(五子衍宗丸) on Antioxidant Capacity in D-galactose Induced Aging Rats (오자연종환(五子衍宗丸)이 노화유발(老化誘發) 흰주의 항산화능(抗酸化能)에 미치는 영향(影響))

  • Kim, Ki-Hong;Ding, Guo-Xun;Kim, Kwang-Ho;Ko, Seong-Gyu
    • Journal of Society of Preventive Korean Medicine
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    • v.9 no.1
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    • pp.49-63
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    • 2005
  • Objectives : Ojayeonjonghwan(五子衍宗丸) is composed of Polygonum multiflorum THUNB, and some medical herbs that are known as formula of senescence delay effects. The purpose of this study is to investigate th effect of Ojayeonjonghwan on antioxidant enzyme activities, such as Thiobarbituric acid reactive substance(TBARS), Superoxide dismutase(SOD), Catalase(CAT), Glutathione preoxidase (GSH-px) in rat erythrocytes and blood plasma. Methods : Sprague-Dawley rats were divided into 3 groups, Normal group (supplied enough water and feeds only, Normal Group), D-galatose administered group(injected D-galatose 50mg/kg, 1time/day for 6 weeks, Control Group) and Ojayeonjonghwan administered group (D-galactose 50mg/kg and Ojayeonjonghwan extracts 245.0mg/200g 1time/day for 6 weeks, OJY Group). Rats were sacrificed and TBARS, SOD, CAT, GSH-px, Plasma total lipid, Plasma triglyceride and cholesterol were measured in rat erythrocytes and blood plasma. Results : TBARS in plasma concentration of OJY group was significantly lower than that of control group. Red blood cell(RBC) SOD activity of OJY group was significantly higher than that of control group(F=16.057, p=0.0001, ANOVA test), RBC GSH-px activity of OJY group was increased(F=4.271, p=0.034, ANOVA test). RBC catalase activities of all experimental group were not significantly different. Total lipid and triglyceride concentration in plasma of all experimental groups were not significantly different. Total cholesterol concentrations in plasma of OJY group were significantly lower than those of control group(F=4.387, p=0.032, ANOVA test). Conclusions : According to the above results, it is considered that Ojayeonjonghwan is effective in inhibiting lipid peroxidation and increasing antioxidative enzyme activities in D-galactose induced aging rat.

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Effect of Hasuohwan(何首烏丸) on Antioxidant Capacity in D-galactose Induced Aging Rats (하수오환(何首烏丸)이 노화(老化)유발 백서(白鼠)의 항산화능에 미치는 영향)

  • Lee Jeong-Won;Lee Song-Shil;Baek Jin-Woong;Lee Sang-Jae;Kim Kwang-Ho
    • Journal of Society of Preventive Korean Medicine
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    • v.8 no.1
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    • pp.115-133
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    • 2004
  • Hasuohwan(何首烏丸) composed of Polygonum multiflorum Thunb and some medical herbs are known as formula of senescence delay effect. The aim of this study is to investigate the effect of Hasuohwan(何首烏丸) on antioxidant enzyme activity such as Thiobarbituric acid reactive substance(TBARS) in rat plasma and liver, Superoxide dismutase(SOD), Glutathione peroxidase(GSH-px), Catalase(CAT) in rat erythrocyte and liver. Rats were sacrificed and TBARS was measured in rat plasma and liver. SOD, GSH-px and CAT were measured in rat erythrocytes and liver. TBARS in plasma concentrations of HSO group was significantly lower than those of control group. RBC and liver GSH-px activities of HSO group were significantly higher than those of control group. According to above results, it is considered that Hasuohwan is effective in inhibiting lipid peroxidation and increasing antioxidative enzyme activities in D-galactose induced aging rat. Therefore, Hsuohwan is considered in effective of senescence delay.

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Effect of Sheep and Chicken Antibodies to Rat Adipocytes Plasma Membranes on Rat Carcass Fat

  • Wang, Jundong;Zhang, Jianfeng;Li, Junping;Hao, Junhu;Wang, Shaolin;Zhang, Jianhai
    • Asian-Australasian Journal of Animal Sciences
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    • v.17 no.8
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    • pp.1177-1182
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    • 2004
  • Polyclonal anti-sera were collected from sheep and chicken immunized with adipocytes plasma membranes. Thirty two male wistar rats, weighing 185-215 grams, were divided randomly into 4 groups (trial 1: control group and treat group, trial 2: control group and treat group), with 8 rats in each group. The experiment lasted for 7 weeks. Trial one: The control group received four consecutive daily intraperitoneal injections of 1ml of sheep normal sera. The same 4 day daily dose of group sheep anti-rats sera adipocyte plasma membrane anti-sera was administered to the treat group. The results showed that the treatment for treat group increased body weight by 6.35% (p<0.05) and food intake by 6.85%, and improved food conversion efficiency (Food intake/gain) by 45.00% (p<0.05). Periernal, epididymal and omental adipose deposit weights were decreased by 23.92% (p<0.05), 34.45% (p<0.05) and 0.98% respectively, while total fat content decreased by 20.92%. Trial two: The control group received four consecutive daily intraperitoneal injections of 1 ml of chicken normal sera, the results of injections of chicken anti-rats sera adipocyte plasma membrane antis-era administered to the treat group indicated that chicken anti-rats adipocyte plasma membranes immunization had an disadvantageous effect on the growth of the wistar rats by the end of 7th wk, compared with the control group. The immunized group decreased in total weight by 40 gram (p<0.05) an averagely and in food intake noticeably (p<0.01). The deposition of fat and the rates of TG and FFA in serum had no statistical significance.