• Title/Summary/Keyword: drug safety

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Development and validation of an analytical method for the quantification of 2,6-diisopropylnaphthalene in agricultural products using GC-MS/MS

  • Lee, Han Sol;Park, Ji-Su;Lee, Su Jung;Shin, Hye-Sun;Chung, Yun mi;Choi, Ha na;Yun, Sang Soon;Jung, Yong-hyun;Oh, Jae-Ho
    • Analytical Science and Technology
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    • v.34 no.1
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    • pp.1-8
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    • 2021
  • An analytical method was developed and optimized for the quantification of a plant growth regulator, 2,6-diisopropylnaphthalene (2,6-DIPN), in agricultural products using gas chromatography-tandem mass spectrometry. The samples were extracted, partitioned, and were purified using a Florisil® cartridge. To validate the analytical method, its specificity, linearity, limit of detection (LOD) and limit of quantification (LOQ) of the instrument, LOQ of the analytical method (MLOQ), accuracy, and repeatability were considered. The method displayed excellent results during validation, and is suitable for the determination and quantification of the low residual levels of the analyte in the agricultural samples. All of the results with the optimized method were satisfactory and within the criteria ranges requested in the Codex Alimentarius Commission guidelines and the Ministry of Food and Drug Safety guidelines for pesticide residue analysis. The developed method is simple and accurate and can be used as a basis for safety management of 2,6-DIPN.

Synthetic Cannabinoid-Induced Immunosuppression Augments Cerebellar Dysfunction in Tetanus-Toxin Treated Mice

  • Yun, Jaesuk;Gu, Sun Mi;Lee, Tac-hyung;Song, Yun Jeong;Seong, Seonhwa;Kim, Young-Hoon;Cha, Hye Jin;Han, Kyoung Moon;Shin, Jisoon;Oh, Hokyung;Jung, Kikyung;Ahn, Chiyoung;Park, Hye-Kyung;Kim, Hyung Soo
    • Biomolecules & Therapeutics
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    • v.25 no.3
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    • pp.266-271
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    • 2017
  • Synthetic cannabinoids are one of most abused new psychoactive substances. The recreational use of abused drug has aroused serious concerns about the consequences of these drugs on infection. However, the effects of synthetic cannabinoid on resistance to tetanus toxin are not fully understood yet. In the present study, we aimed to determine if the administration of synthetic cannabinoids increase the susceptibility to tetanus toxin-induced motor behavioral deficit and functional changes in cerebellar neurons in mice. Furthermore, we measured T lymphocytes marker levels, such as CD8 and CD4 which against tetanus toxin. JWH-210 administration decreased expression levels of T cell activators including cluster of differentiation (CD) $3{\varepsilon}$, $CD3{\gamma}$, CD74p31, and CD74p41. In addition, we demonstrated that JWH-210 induced motor impairment and decrement of vesicle-associated membrane proteins 2 levels in the cerebellum of mice treated with tetanus toxin. Furthermore, cerebellar glutamatergic neuronal homeostasis was hampered by JWH-210 administration, as evidenced by increased glutamate concentration levels in the cerebellum. These results suggest that JWH-210 may increase the vulnerability to tetanus toxin via the regulation of immune function.

Potential for Dependence on Lisdexamfetamine - In vivo and In vitro Aspects

  • Yun, Jaesuk;Lee, Kwang-Wook;Eom, Jang-Hyeon;Kim, Young-Hoon;Shin, Jisoon;Han, Kyoungmoon;Park, Hye-Kyung;Kim, Hyung Soo;Cha, Hye Jin
    • Biomolecules & Therapeutics
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    • v.25 no.6
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    • pp.659-664
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    • 2017
  • Although lisdexamfetamine is used as a recreational drug, little research exists regarding its potential for dependence or its precise mechanisms of action. This study aims to evaluate the psychoactivity and dependence profile of lisdexamfetamine using conditioned place preference and self-administration paradigms in rodents. Additionally, biochemical techniques are used to assess alterations in the dopamine levels in striatal synaptosomes following administration of lisdexamfetamine. Lisdexamfetamine increased both conditioned place preference and self-administration. Moreover, after administration of the lisdexamfetamine, dopamine levels in the striatal synaptosomes were significantly increased. Although some modifications should be made to the analytical methods, performing high performance liquid chromatography studies on synaptosomes can aid in predicting dependence liability when studying new psychoactive substances in the future. Collectively, lisdexamfetamine has potential for dependence possible via dopaminergic pathway.

Cardiovascular Safety Pharmacology of Sibutramine

  • Yun, Jaesuk;Chung, Eunyong;Choi, Ki Hwan;Cho, Dae Hyun;Song, Yun Jeong;Han, Kyoung Moon;Cha, Hey Jin;Shin, Ji Soon;Seong, Won-Keun;Kim, Young-Hoon;Kim, Hyung Soo
    • Biomolecules & Therapeutics
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    • v.23 no.4
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    • pp.386-389
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    • 2015
  • Sibutramine is an anorectic that has been banned since 2010 due to cardiovascular safety issues. However, counterfeit drugs or slimming products that include sibutramine are still available in the market. It has been reported that illegal sibutramine-contained pharmaceutical products induce cardiovascular crisis. However, the mechanism underlying sibutramine-induced cardiovascular adverse effect has not been fully evaluated yet. In this study, we performed cardiovascular safety pharmacology studies of sibutramine systemically using by hERG channel inhibition, action potential duration, and telemetry assays. Sibutramine inhibited hERG channel current of HEK293 cells with an $IC_{50}$ of $3.92{\mu}M$ in patch clamp assay and increased the heart rate and blood pressure ($76{\Delta}bpm$ in heart rate and $51{\Delta}mmHg$ in blood pressure) in beagle dogs at a dose of 30 mg/kg (per oral), while it shortened action potential duration (at $10{\mu}M$ and $30{\mu}M$, resulted in 15% and 29% decreases in $APD_{50}$, and 9% and 17% decreases in $APD_{90}$, respectively) in the Purkinje fibers of rabbits and had no effects on the QTc interval in beagle dogs. These results suggest that sibutramine has a considerable adverse effect on the cardiovascular system and may contribute to accurate drug safety regulation.

Detection of CTX-M Type ESBL Producing Salmonella in Retail Meat in Korea

  • Kim, Yong Hoon;Joo, In Sun;Kim, Yoon Jeong;Oh, Mi Hyun;Cho, Joon Il;Han, Min Kyong;Kim, Soon Han;Moon, Tae Wha;Park, Kun Sang
    • Journal of Food Hygiene and Safety
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    • v.29 no.1
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    • pp.47-52
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    • 2014
  • This study was performed to evaluate antimicrobial resistance of food-borne pathogens isolated from retail meat in Korea. A total of 157 samples of beef, pork, and chicken were collected and analyzed for E. coli, Salmonella, Campylobacter. Resistances to tetracycline were declined in accord with reduced usage of tetracycline in live stock production. E. coli stains from chicken meat had higher multi-drug resistance ratio than strains from other meat. One extended spectrum beta lactamase (ESBL) producing E. coli and two ESBL producing Salmonella were identified in this study. ESBL producing Salmonella strains were confirmed to carry CTX-M-1 type genes.

Application and Validation of an Optimal Analytical Method using QuEChERS for the determination of Tolpyralate in Agricultural Products (QuEChERS법을 활용한 농산물 중 제초제 Tolpyralate의 최적 분석법 선발 및 검증)

  • Lee, Han Sol;Park, Ji-Su;Lee, Su Jung;Shin, Hye-Sun;Kim, Ji-Young;Yun, Sang Soon;Jung, Yong-hyun;Oh, Jae-Ho
    • Korean Journal of Environmental Agriculture
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    • v.39 no.3
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    • pp.246-252
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    • 2020
  • BACKGROUND: Pesticides are broadly used to control weeds and pests, and the residues remaining in crops are managed in accordance with the MRLs (maximum residue limits). Therefore, an analytical method is required to quantify the residues, and we conducted a series of analyses to select and validate the quick and simple analytical method for tolpyralate in five agricultural products using QuEChERS (quick, easy, cheap, effective, rugged and safe) method and LC-MS/MS (liquid chromatography-tandem mass spectrometry). METHODS AND RESULTS: The agricultural samples were extracted with acetonitrile followed by addition of anhydrous magnesium sulfate, sodium chloride, disodium hydrogencitrate sesquihydrate and trisodium citrate dihydrate. After shaking and centrifugation, purification was performed with d-SPE (dispersive-solid phase extraction) sorbents. To validate the optimized method, its selectivity, linearity, LOD (limit of detection), LOQ (limit of quantitation), accuracy, repeatability, and reproducibility from the inter-laboratory analyses were considered. LOQ of the analytical method was 0.01 mg/kg at five agricultural products and the linearity of matrix-matched calibration were good at seven concentration levels, from 0.0025 to 0.25 mg/L (R2≥0.9980). Mean recoveries at three spiking levels (n=5) were in the range of 85.2~112.4% with associated relative standard deviation values less than 6.2%, and the coefficient of variation between the two laboratories was also below 13%. All optimized results were validated according to the criteria ranges requested in the Codex Alimentarius Commission (CAC) and Ministry of Food and Drug Safety (MFDS) guidelines. CONCLUSION: In conclusion, we suggest that the selected and validated method could serve as a basic data for detecting tolpyralate residue in imported and domestic agricultural products.

Enhancement of Analytical Method for Thidiazuron Residues and Monitoring of its Residues in Agricultural Commodities (농산물 중 thidiazuron 잔류분석법 개선 및 잔류실태 조사)

  • Do, Jung-Ah;Lee, Mi-Young;Park, Hyejin;Kwon, Ji-Eun;Cho, Yoon-Jae;Chang, Moon-Ik;Oh, Jae-Ho;Hong, Jin-Hwan
    • Korean Journal of Environmental Agriculture
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    • v.32 no.3
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    • pp.207-213
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    • 2013
  • BACKGROUND: This study was conducted to develop analytical method with reproducibility, accuracy and applicability to agricultural products than the existing methods. METHODS AND RESULTS: Mean recoveries of thidiazuron ranged from 89.2 to 91.2 in hulled rices, 87.2 to 92.1 in peppers, from 76.4 to 86.9 in potatoes, from 91.2 to 95.7 in watermelons, from 86.5 to 88.5 in kiwi fruits, and from 89.5 to 94.0 in grapes, with less than 10% of relative standard deviations. In addition, the limit of quantitation was set to be 0.05 mg/kg and there were no interfering peaks in integrating the thidiazuron peak. CONCLUSION(S): These results represent that the enhanced analytical method has reliable accuracy, precision, selectivity, and sensitivity.

Multi-class, Multi-residue Analysis of 59 Veterinary Drugs in Livestock Products for Screening and Quantification Using Liquid Chromatography-tandem Mass Spectrometry

  • Yu Ra Kim;Sun Young Park;Tae Ho Lee;Ji Young Kim;Jang-Duck Choi;Guiim Moon
    • Korean Journal of Environmental Agriculture
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    • v.41 no.4
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    • pp.288-309
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    • 2022
  • BACKGROUND: The objective of this study was to develop a comprehensive and simple method for the simultaneous determination of 59 veterinary drug residues in livestock products for safety management. METHODS AND RESULTS: For sample preparation, we used a modified liquid extraction method, according to which the sample was extracted with 80% acetonitrile followed by incubation at -20℃ for 30 min. After centrifugation, an aliquot of the extract was evaporated to dryness at 40℃ and analyzed using liquid chromatography combined with tandem mass spectrometry. The method was validated at three concentration levels for beef, pork, chicken, egg, and milk in accordance with the Codex Alimentarius Commission/Guidelines 71-2009. Quantitative analysis was performed using a matrix-matched calibration. As a results, at least 52 (77.6%) out of 66 compounds showed the proper method validation results in terms of both recovery of the target compound and coefficient of variation required by Codex guidelines in livestock products. The limit of quantitation of the method ranged from 0.2 to 1119.6 ng g-1 for all matrices. CONCLUSION(S): This method was accurate, effective, and comprehensive for 59 veterinary drugs determination in livestock products, and can be used to investigate veterinary drugs from different chemical families for safety management in livestock products.

Dependence Potential of Tramadol: Behavioral Pharmacology in Rodents

  • Cha, Hye Jin;Song, Min Ji;Lee, Kwang-Wook;Kim, Eun Jung;Kim, Young-Hoon;Lee, Yunje;Seong, Won-Keun;Hong, Sa-Ik;Jang, Choon-Gon;Yoo, Han Sang;Jeong, Ho-Sang
    • Biomolecules & Therapeutics
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    • v.22 no.6
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    • pp.558-562
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    • 2014
  • Tramadol is an opioid analgesic agent that has been the subject of a series of case reports suggesting potential for misuse or abuse. However, it is not a controlled substance and is not generally considered addictive in Korea. In this study, we examined the dependence potential and abuse liability of tramadol as well as its effect on the dopaminergic and serotonergic systems in rodents. In animal behavioral tests, tramadol did not show any positive effects on the experimental animals in climbing, jumping, and head twitch tests. However, in the conditioned place preference and self-administration tests, the experimental animals showed significant positive responses. Taken together, tramadol affected the neurological systems related to abuse liability and has the potential to lead psychological dependence.