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공태연,김소연 한국고분자학회 2021 한국고분자학회 학술대회 연구논문 초록집 Vol.46 No.2
Polymer nanocomposites (PNCs), incorporating nanoparticles into a polymer matrix, generally enhance physical properties compared to neat polymers. As the mechanical reinforcement of PNCs relies on particle dispersion, many studies have been conducted changing basic characteristics of the polymer matrix, such as compatibility with particles, chain rigidity, and polymer molecular weight (MW). However, these studies mostly focused on the PNCs with a unimodal MW of polymer matrix. In this study, we investigate the microstructure and rheological properties of PNC made of a homopolymer blend matrix but with bimodal MW distribution and compare its property to that of a unimodal matrix. In the case of PNC with MW blends, the nanoparticles are readily aggregated regardless of the nanoparticle content, which lead to a dramatic increase of shear modulus up to ~500 times compared to that of PNC with unimodal MW.
Liquid Chromatography-tandem Mass Spectrometry for Quantification of Dioscin in Rat Plasma
공태연,지혜영,최상진,손미원,이혜숙 사단법인 한국질량분석학회 2013 Mass spectrometry letters Vol.4 No.3
Dioscin is a biologically active steroidal saponin with anticancer and hepatoprotective effects. A rapid, selective, andsensitive liquid chromatographic method with electrospray ionization tandem mass spectrometry was developed for the quantificationof dioscin in rat plasma. Dioscin was extracted from rat plasma using ethyl acetate at acidic pH. The analytes were separatedon a Halo C18 column using gradient elution of acetonitrile and 0.1% formic acid and detected by tandem massspectrometry in selected reaction monitoring mode. The standard curve was linear (r2 = 0.998) over the concentration range of1−100 ng/mL. The lower limit of quantification was 1.0 ng/mL using 50 μL of plasma sample. The coefficient of variation andrelative error for intra- and inter-assay at four QC levels were 1.3 to 8.0% and −5.4 to 10.0%, respectively. This method wasapplied successfully to the pharmacokinetic study of dioscin after oral administration of dioscin at a dose of 29.2 mg/kg in maleSprague-Dawley rats.
공태연,김주현,권순상,정재철,김희승,인문교,이혜숙 대한약학회 2017 Archives of Pharmacal Research Vol.40 No.6
MAM-2201, a synthetic cannabinoid, is a potentagonist of the cannabinoid receptors and is increasinglyused as an illicit recreational drug. The inhibitory effects ofMAM-2201 on major drug-metabolizing enzymes such ascytochrome P450s (CYPs) and uridine 50-diphospho-glucuronosyltransferases(UGTs) have not yet been investigatedalthough it is widely abused, sometimes incombination with other drugs. We evaluated the inhibitoryeffects of MAM-2201 on eight major human CYPs (CYPs1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, and 3A4) and sixUGTs (UGTs 1A1, 1A3, 1A4, 1A6, 1A9, and 2B7) ofpooled human liver microsomes; we thus explored potentialMAM-2201-induced drug interactions. MAM-2201potently inhibited CYP2C9-catalyzed diclofenac 40-hydroxylation,CYP3A4-catalyzed midazolam 10-hydroxylation,and UGT1A3-catalyzed chenodeoxycholic acid24-acyl-glucuronidation, with Ki values of 5.6, 5.4 and5.0 lM, respectively. MAM-2201 exhibited mechanismbasedinhibition of CYP2C8-catalyzed amodiaquine N-deethylationwith Ki and kinact values of 1.0 lM and0.0738 min-1, respectively. In human liver microsomes,MAM-2201 (50 lM) negligibly inhibited CYP1A2,CYP2A6, CYP2B6, CYP2C19, CYP2D6, UGT1A1,UGT1A4, UGT1A6, UGT1A9, and UGT2B7. Based onthese in vitro results, we conclude that MAM-2201 has thepotential to trigger in vivo pharmacokinetic drug interactionswhen co-administered with substrates of CYP2C8,CYP2C9, CYP3A4, and UGT1A3.
Synthetic cannabinoids are substrates and inhibitors of multiple drug-metabolizing enzymes
공태연,김주현,김동균,이혜숙 대한약학회 2018 Archives of Pharmacal Research Vol.41 No.7
Synthetic cannabinoids, a new class of psychoactivesubstances, are potent agonists of cannabinoidreceptors, which mimic the psychoactive effects of theprincipal psychoactive component of cannabis, D9-tetrahydrocannabinol. Despite governmental scheduling asillicit drugs, new synthetic cannabinoids are being produced. The abuse of synthetic cannabinoids with severaldrugs containing different chemical groups has resulted inlarge numbers of poisonings. This has increased theurgency for forensic and public health laboratories toidentify the metabolites of synthetic cannabinoids and applythis knowledge to the development of analytical methodsand for toxicity prediction. It is necessary to determinewhether synthetic cannabinoids are involved in drug-metabolizingenzyme-mediated drug–drug interactions. Thisreview describes the metabolic pathways of 13 prevalentsynthetic cannabinoids and various drug-metabolizingenzymes responsible for their metabolism, including cytochromeP450 (CYP), UDP-glucuronosyltransferases(UGTs), and carboxylesterases. The inhibitory effects ofsynthetic cannabinoids on CYP and UGT activities are alsoreviewed to predict the potential of synthetic cannabinoidsfor drug–drug interactions. The drug-metabolizing enzymesresponsible for metabolism of synthetic cannabinoidsshould be characterized and the effects of syntheticcannabinoids on CYP and UGT activities should be determinedto predict the pharmacokinetics of syntheticcannabinoids and synthetic cannabinoid-induced drug–druginteractions in the clinic.
공태연,김주현,김진영,인문교,최경호,김희승,이혜숙 대한약학회 2017 Archives of Pharmacal Research Vol.40 No.2
Liquid chromatography-tandem mass spectrometricmethod for analysis of 113 abuse drugs and theirmetabolites in human urine was developed and validated. Asimple sample clean-up procedure using the ‘‘dilute andshoot’’ approach, followed by reversed phase separation,provided a fast and reliable method for routine analysis. Drugs were separated in a Capcell Pak MG-III C18 columnusing a gradient elution of 1 mM ammonium formate with0.1% formic acid in water and acetonitrile. The total timefor analysis was 32 min. The multiple reaction monitoringmode using two transitions (e.g., quantifier and qualifier)was optimized for both identification and determination. The calibration curves for each analyte were linear over theconcentration ranges of 1–100, 5–100, or 10–100 ng/mLusing 400 lL of human urine sample with the coefficient ofdetermination above 0.9921. The coefficient of variationand accuracy for the intra- and inter-assays of the testeddrugs at three QC levels were 1.1–14.6 and 86.7–106.8%,respectively. The present method was successfully appliedto the analysis of forensic urine samples obtained from 17drug abusers. This method is useful for the rapid andaccurate determination of multiple drug abuse with a smallamount of urine in forensic and clinical toxicology.
Comparative metabolism of honokiol in mouse, rat, dog, monkey, and human hepatocytes
정현욱,김주현,공태연,최원구,이혜숙 대한약학회 2016 Archives of Pharmacal Research Vol.39 No.4
Honokiol has antitumor, antioxidative, anti-inflammatory,and antithrombotic effects. Here we aimed toidentify the metabolic profile of honokiol in mouse, rat,dog, monkey, and human hepatocytes and to characterizethe enzymes responsible for the glucuronidation and sulfationof honokiol. Honokiol had a high hepatic extractionratio in all five species, indicating that it was extensivelymetabolized. A total of 32 metabolites, including 17common and 15 different metabolites, produced via glucuronidation,sulfation, and oxidation of honokiol allylgroups were tentatively identified using liquid chromatography–high resolution quadrupole Orbitrap mass spectrometry. Glucuronidation of honokiol to M8 (honokiol-4-glucuronide) and M9 (honokiol-20-glucuronide) was thepredominant metabolic pathway in hepatocytes of all fivespecies; however, interspecies differences between 4- and20-glucuronidation of honokiol were observed. UGT1A1,1A8, 1A9, 2B15, and 2B17 played major roles in M8formation, whereas UGT1A7 and 1A9 played major rolesin M9 formation. Human cDNA-expressed SULT1C4played a major role in M10 formation (honokiol-20-sulfate),whereas SULT1A1*1, 1A1*2, and 1A2 played major rolesin M11 formation (honokiol-4-sulfate). In conclusion,honokiol metabolism showed interspecies differences.