• Title/Summary/Keyword: Drug monitoring

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Identification of Pitfalls Related to the Analysis of Liquid Chromatography-Tandem Mass Spectrometry and Liquid Chromatography-Time of Flight Mass Spectrometry (액체크로마토그래프-질량분석기를 이용한 정성 및 정량 오류의 확인)

  • Kwon, Jin-Wook;Cho, Yoon-Jae;Rhee, Gyu-Seek
    • Korean Journal of Environmental Agriculture
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    • v.34 no.3
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    • pp.230-237
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    • 2015
  • BACKGROUND: To identify the sources of inaccuracy in LC/MS/MS methods used in the routine quantitation of small molecules are described and discussed. METHODS AND RESULTS: Various UPLC coupled to triple quadrupole mass spectrometer and time of flight (TOF) were used to identify the potential sources of inaccuracy and inducing the pitfalls of qualification and quntitation during the veterinary drug residue analysis. Some of stable isotope labelled veterinary drugs, which were used as internal standards, presented "cross-talk", regardless of manufactures of mass spectrometer and types of spectrometer. Group of sulfonamides also presented inaccuracy qualification and quantitation due to the multi-residue analytical method with the same fragment ions at the close retention times. CONCLUSION: The phenomena of "cross-talk" occurring between subsequently monitored transition from stable isotope labelled and isotope non-labelled authentic chemical were identified. To prevent errors and achieve more accurate data during the analysis of small molecules by LC/MS/MS SRM method, Followings should be taken care of and kept checking; purity and concentration of stable isotope as an internal standard, prevention of carry-over during the separation in column, minimizing the ion suppression by matrix effect, identification of retention time, precursor ion and product ion, and full knowledge of data processing including smoothing and peak integration.

Monitoring of Veterinary Medicine Residues in Honey (벌꿀 중 동물용의약품 잔류량 모니터링)

  • Kang, Eun-Gui;Jung, Yung-Hyeun;Jung, Ji-Hye;Kim, Mi-Ran;Lee, Kyung-Jin;Jung, Jin-Joo;Park, Jong-Seok;Bahn, Kyeong-Nyeo;Jang, Young-Mi;Kang, Chan-Soon
    • Korean Journal of Food Science and Technology
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    • v.42 no.6
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    • pp.643-647
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    • 2010
  • This research was carried out to investigate residues of neomycin, streptomycin, dihydrostreptomycin, amitraz, 2,4-dimethylaniline (one of amitraz's metabolites), and coumaphos in honey in order to intensively control their use following the establishment of Korean maximum residue limits (MRLs) for veterinary drugs in honey in 2007. To monitor for residues, 110 honeys and food products with honey were collected and analyzed. The collected honeys included acasia, mixed flower, chestnut, rape flower, jujube, and native types. Neomycin, streptomycin, dihydrostreptomycin, oxytetracycline, and amitraz were not detected among samples. Coumaphos was found in the Korean acasia honey at 0.02 mg/kg, but its concentration was under the MRL (0.1 mg/kg) for coumaphos. According to the results, there were no violations of the Korean MRLs of veterinary drugs in honey.

Real-Time Monitoring of Mitochondrial ATP Synthesis and Hydrolysis by Surface Infrared Spectroscopy

  • Yamaguchi, Ryo-Taro;Hirano-Iwata, Ayumi;Aonuma, Yuki;Yoshimura, Yuya;Shinohara, Yasuo;Kimura, Yasuo;Niwano, Michio
    • Proceedings of the Korean Vacuum Society Conference
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    • 2013.02a
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    • pp.108-109
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    • 2013
  • Mitochondria play key roles in the production of cell's energy. Their dominant function is the synthesis of adenosine 5'-triphosphate (ATP) from adenosine diphosphate (ADP) and phosphate (Pi) through the oxidative phosphorylation. Evaluation of drug-induced mitochondrial toxicity has become increasingly important since mitochondrial dysfunction has recently been implicated in numerous diseases including cancer and diabetes mellitus. Mitochondrial functions have been monitored via oxygen consumption, mitochondrial membrane potential, and more importantly via ATP synthesis since ATP synthesis is the most essential function of mitochondria. Various analytical methods have been employed to investigate ATP synthesis in mitochondria, including high performance liquid chromatography (HPLC), bioluminescence technique, and pH measurement. However, most of these methods are based on destructive analysis or indirect monitoring through the enzymatic reaction. Infrared absorption spectroscopy (IRAS) is one of the useful techniques for real-time, label-free, and direct monitoring of biological reactions [1,2]. However, the strong water absorption requires very short path length in the order of several micrometers. Transmission measurements with thin path length are not suitable for mitochondrial assays because solution handlings necessary for evaluating mitochondrial toxicity, such as rapid mixing of drugs and oxygen supply, are difficult in such a narrow space. On the other hand, IRAS in the multiple internal reflection (MIR) geometry provides an ideal optical configuration to combine solution handling and aqueous-phase measurement. We have recently reportedon a real-time monitoring of drug-induced necrotic and apoptotic cell death using MIR-IRAS [3,4]. Clear discrimination between viable and damaged cells has been demonstrated, showing a promise as a label-free and real-time detection for cell-based assays. In the present study, we have applied our MIR-IRAS system to mitochondria-based assays by monitoring ATP synthesis in isolated mitochondria from rat livers. Mitochondrial ATP synthesis and hydrolysis were in situ monitored with MIR-IRAS, while dissolved oxygen level and solution pH were simultaneously monitored with O2 and pH electrodes, respectively. It is demonstrated that ATP synthesis and hydrolysis can be monitored by the IR spectral changes in phosphate groups in adenine nucleotides and MIR-IRAS is useful for evaluating time-dependent drug effects of mitochondrial toxicants.

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Isolation of Hepatic Drug Metabolism Inhibitors from the Seeds of Myristica fragrans

  • Shin, Kuk-Hyun;Kim, Ok-Nam;Woo, Won-Sick
    • Archives of Pharmacal Research
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    • v.11 no.3
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    • pp.240-243
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    • 1988
  • The hexane extract from Nutmeg, the seed of Myristica fragrans significantly inhibited hepatic drug-metabolizing enzyme activity. Through systematic fractionation by $SiO_2$ column and vacuum liquid chromatography monitoring by bioassay, three components, myristicin, (I), licarin-B (II) and dehydrodiisoeugenol (III) were isolated as active principles. Compounds II and III, with a single treatment (200mg/kg, i.p.) showed not only a significant prolongation of hexobarbital-induced sleeping time but also a significant inhibition of aminopyrine N-demethylase and hexobarbital hydroxylase activities in mice. Compounds I and II provoked a sleep episode at a subhypnotic dose of HB, suggesting that they possess CNS-depressant properties.

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Strategy to Overcome Drug Resistance That Develops during Treatment of Chronic Hepatitis B in Children

  • Hong, Suk Jin;Choe, Byung-Ho
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.15 no.2
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    • pp.63-73
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    • 2012
  • Development of antiviral resistance to lamivudine is the most important factor for the treatment failure. It is necessary to establish proper guidelines to overcome drug resistance for children with chronic hepatitis B. Primary treatment with lamivudine should be considered if patients are in immune-clearance phase and have persistently elevated ALT levels more than twice the upper limit of normal value. Before initiating the therapy, careful consideration of the patient's status is required to exclude abnormal liver function tests due to other causes. The treatment option should be carefully decided to suppress the viral replication effectively. To obtain good compliance, clinicians should educate patients and their parents. Appropriate monitoring for virologic breakthrough and genotypic resistance is important in deciding to change the treatment plan. Sequential monotherapy should be avoided and a combination of drugs in other categories is recommended. New antiviral agents, such as entecavir and tenofovir, which have high potency and high genetic barrier, are soon expected to be available for use with children.

Hepatic Drug Metabolism Modifier from Arils of Myristica fragrans

  • Shin, Kuk-Hyun;Woo, Won-Sick
    • Korean Journal of Pharmacognosy
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    • v.17 no.1
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    • pp.91-99
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    • 1986
  • The single treatment of mice with steam distillate, non-volatile ether extract and methanol extract from mace (Arils of Myristica fragrans) caused a significant prolongation of hexobarbital-induced narcosis and increase in strychnine toxicity as well as a significant decrease in hepatic microsomal drug metabolizing enzyme activities. On 7 consecutive daily administrations, however, the duration of hypnosis was markedly shortened and significant increases in the hepatic enzyme activities were shown. With systematic fractionation by $SiO_2$ column chromatography of non-volatile ether fraction monitoring by animal tests a new lignan (mp $70{\sim}72^{\circ}$, MW 328, $[{\alpha}]^{20}_D+5.28$) was isolated as an active principle and its structure was elucidated as (2R, 3S)-1-(3,4-methylendioxyphenyl)-2,3 dimethyl-4-(4-hydroxy-3-methoxyphenyl) butane.

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Chemical Residues in Edible Tissues of Animals and Control Measures (축산식품의 유해물질 잔류와 그 관리방안)

  • 박종명;박근식
    • Journal of Food Hygiene and Safety
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    • v.6 no.2
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    • pp.17-22
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    • 1991
  • Great attention form a public health aspect has centered on the safety of tissues residues of veterinary drugs and environmental contaminants, with intensification of animal husbandry, the use of veterinary drugs will become increasingly important. Heavy responsibility is placed on the veterinarian and livestock producer to observe the period for withdrawal of drug prior to slaughter to assure that illegal concentrations of drug residues in meat, milk and egg do not occur. Every nation has their own regulations in relation to the residues and the guidelines on the use of veterinary drugs to fulfil the regulations, and their own national residue programs to monitoring and eliminate illegal products. Good practice of veterinary drug by users and governmental surveillance programs are very important to ensure animal food safety.

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Drug Interaction Between Phenytoin and Diltiazem in Rabbit (딜티아젬과 페니토인과의 약물상호작용)

  • Choi, Jun-Shik;Chang, Il-Hyo
    • Journal of Pharmaceutical Investigation
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    • v.23 no.1
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    • pp.27-32
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    • 1993
  • Pharmacokinetic drug interaction between phenytoin and diltiazem was investigated following i.v. administration concomitantly to rabbits. Diltiazem was coadministered at doses of 1, 2 and 3 mg/kg, respectively, with phenytoin (5 mg/kg) to rabbits. Plasma concentration and AUC of phenytoin were increased significantly, but volume of distribution and total body clearance were decreased significantly (p<0.05) at doses of 2 mg and 3 mg/kg of diltiazem. From the results of this experiment, it is desirable that dosage regimen of phenytoin should be adjusted and that therapeutic drug monitoring should be practiced for reduction of side or toxic effect when phenytoin should be administered with diltiazem in clinical practice.

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Effect of the Constituents of Angelicae dahuricae Radix on Hepatic Drug Metabolizing Enzyme Activity (백지근(白芷根) 성분(成分)이 간(肝)의 약물대사효소활성(藥物代謝酵素活性)에 미치는 효과(效果))

  • Shin, Kuk-Hyun;Kim, Ok-Nam;Woo, Won-Sick
    • Korean Journal of Pharmacognosy
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    • v.19 no.1
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    • pp.19-27
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    • 1988
  • The hexane and ether extracts from the roots of Angelica dahurica caused a significant inhibition of hepatic drug-metabolizing enzyme (DME) activity. Through systematic fractionation by $SiO_2\;column$ and vacuum liquid chromatography monitoring by bioassays, three furanocoumarins, phellopterin, byakangelicin and tert-O-methylbyakangelicin were isolated as active principles. These components have biphasic responses, both inhibitory and inducing effects on DME system. Tert-O-methyl byakangelicin was found to have the strongest enzyme inhibitory potency.

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