• Title/Summary/Keyword: Pharmaceutical Compounds

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Simultaneous determination of illegal galactagogue adulterants in supplement diets by LC-MS/MS

  • Lee, Ji Hyun;Cho, So-Hyun;Park, Han Na;Park, Hyoung Joon;Kim, Nam Sook;Park, Sung Kwan;Kang, Hoil
    • Analytical Science and Technology
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    • v.31 no.4
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    • pp.171-178
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    • 2018
  • Recently, for successful lactation, many breastfeeding mothers seek various products, including herbal medicine, dietary supplements, and prescribed medicines, to improve milk production. As demand for galactogogues grows, it is highly possible that pharmaceutical galactogogues may be adulterated with illegal products to maximize their efficacy. For continuous control and supervision of illegal products, we developed and validated a simple and sensitive LC-MS/MS method capable of simultaneously determining five galactogogues. Chromatographic separation was conducted using an Agilent Poroshell $120SB-C_{18}$ column with a mobile phase consisting of 20 mM ammonium formate (pH 5.4) and 100 % acetonitrile. The total run time was 13 min per analyte. The proposed method was performed according to the guidelines of the International Conference of Harmonization and it produced reliable results. This method showed high sensitivity and specificity, with a limit of detection (LOD) and limit of quantitation (LOQ) of 0.01-0.82 ng/mL and 0.02-2.45 ng/mL, respectively, for the solid- and liquid-type samples. Specificity was evaluated by analyzing matrix-blank samples spiked with the target compounds at LOQ levels, which provided a good separation of all peaks without interference. Additionally, the repeatability and intermediate precision were typically <15 %, whereas the recovery was 80-120 % of the values obtained using blank samples. Thus, we concluded that this method could be used for the identification and quantification of galactogogues in food or herbal products.

Optimization of LC-MS/MS for the Analysis of Sulfamethoxazole by using Response Surface Analysis (반응표면분석법을 이용한 설파메톡사졸의 액체크로마토그래프-텐덤형 질량분석 최적화)

  • Bae, Hyo-Kwan;Jung, Jin-Young
    • Journal of Korean Society of Environmental Engineers
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    • v.31 no.9
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    • pp.825-830
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    • 2009
  • Pharmaceutical compounds enter the water environment through the diverse pathways. Because their concentration in the water environment was frequently detected in the level of ppt to ppb, the monitoring system should be optimized as much as possible for finding appropriate management policies and technical solutions. One Factor At a Time (OFAT) approach approximating the response with a single variable has been preferred for the optimization of LC-MS/MS operational conditions. However, it is common that variables in analytical instruments are interdependent. Therefore, the best condition could be found by using the statistical optimization method changing multiple variables at a time. In this research, response surface analysis (RSA) was applied to the LC-MS/MS analysis of emerging antibiotic compound, sulfamethoxazole, for the best sensitivity. In the screening test, fragmentation energy and collision voltage were selected as independent variables. They were changed simultaneously for the statistical optimization and a polynomial equation was fit to the data set. The correlation coefficient, $R^2$ valuerepresented 0.9947 and the error between the predicted and observed value showed only 3.41% at the random condition, fragmentation energy of 60 and collision voltage of 17 eV. Therefore, it was concluded that the model derived by RSA successfully predict the response. The optimal conditions identified by the model were fragmentation energy of 116.6 and collision voltage of 10.9 eV. This RSA can be extensively utilized for optimizing conditions of solid-phase extraction and liquid chromatography.

Distribution of Acriflavine in Rats Following Intramuscular Administration of a Mixture of Acriflavine and Guanosine, a Potential Antitumor Agent (신규 항암성 화합물 아크리플라빈과 구아노신 복합체를 흰쥐에 근육주사시 아크리플라빈의 체내분포)

  • Song, Suk-Gil;Chung, Youn-Bok
    • YAKHAK HOEJI
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    • v.50 no.1
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    • pp.8-14
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    • 2006
  • A 1 : 1 mixture of acriflavine (ACF; CAS 8063-24-9) and guanosine is currently being evaluated as a possible antitumor agent in preclinical studies. Guanosine is known to potentiate the anticancer activity of some compounds. However, the distributions of trypaflavine (TRF) or proflavine (PRF) have not been investigated in mammals. We, therefore, investigated the distribution of TRF and PRF after i.m. administration of the combination mixture (ACF and guanosine) at a dose of 30 mg/kg ACF in rats. to analyze TRF and PRF levels in biological samples, we used an HPLC-based method. The calibration curves for TRF and PRF in the samples were linear over the concenration range of $0.05{\sim}200\;{\mu}g/ml$. The intra- and inter-day assay accuracies of this method were within ${\pm}15\%$ of norminal values and the precision did not exceed $15\%$ of relative standard diviation. The lower limits of quantitation were 50 ng/ml for both TRF and PRF. The distribution of TRF or PRF was determined by 48 h after i.m. administration of the combination mixture at a dose of 30 mg/kg ACF. TRF and PRF were distributed as the following order; kidney>lung>liver>small intestine>muscle. Of the various tissues, TRF and PRF were mainly distributed to the kidney and lung. The concentrations of TRF or PRF in the tissues 24 h after i.m. administration decreased to undetectable levels. The concentrations of TRF or PRF in the blood cells were comparable to those for the plasma. However, the concentrations of TRF or PRF in the both plasma and blood cells 12 h after i.m. administration were not detected. The number of the platelets in the 1 ml of the blood was calculated to be $0.183{\times}10^8/ml$ of blood. The PRF concentration in platelets was higher than that of TRF at initial times after i.m. administration of the combination mixture. However, both the TRF and PRF concentrations in the plateles 24 h after i.m. administration of the combination mixture were below the quantifiable limit. In conclusion, the concentrations of TRF or PRF in the various tissues, plasma, blood cells, and plateles decreased to undetectable levels 24 h after i.m. administration of the combination mixture at a dose of 30 mg/kg ACF.

Comparison of in Vivo Antibacterial Activities and Pharmacokinetics of New Carbapenem Derivatives, CRB 529 and CRB 550, in Mice and Rats (신규 Carbapenem 유도체 CRB 529 및 CRB 550의 생체내 항균효과와 약물동태의 비교)

  • 김준겸;민관기;이주몽;이홍우;김정우
    • YAKHAK HOEJI
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    • v.39 no.4
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    • pp.360-366
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    • 1995
  • 1-$\beta$-Methyl carbapenem-2-substituted pyrroudine derivatives. CRB 529 and CRB 550, were synthesized as investigational carbapenem derivatives. It has been reported that the in vitro antibacterial activities of the compounds against G(+) and G(-) bacteria were almost the same or more effective than those of imipenem (IPM) and meropenem (MEPM), and also showed better in vivo efficacy than MEPM and inlipeneni/cilastatin (IPM/CS) against representative G(-) organisms, P. aeruginosa and MRSA organisms, S. aureus. The antibacterial activities, pharmacokinetics and protective efficacy of IPM/CS and CRB 529 and CRB 550 wereconducted after subcutaneous or intravenous administration to mice and rats. The pharmacokinetic parameters of CRB 529 and CRB 550 in mice were as follows: the observed maximal serum concentrations (C$_{max}$) following I.V. administration were 87.5 and 101 $\mu\textrm{g}$/ml for CRB 529 and CRB 550, respectively, and 63.6 $\mu\textrm{g}$/ml for IPM/CS. The half-lives (t$_{1/2}$) were 14.0 and 12.0 n-dn for CRB 529 and CRB 550, respectively, and 14.8 min for IPM/CS. In rats, $C_{max}$ after I.V. administration were 74.0 and 91.8 $\mu\textrm{g}$/ml for CRB 529 and CRB 550, respectively, and 41.2 $\mu\textrm{g}$/ml for IPM/CS. The tissue levels of CRB 529 and CRB 550 and IPM/CS after I.V. administration at a dose of 20 mg/kg decreased by the following order: lung, heart, kindney, liver and spleen for CRB 529, lddney, liver. lung, heart and spleen for CRB 550 and kidney, lung, liver, heart, spleen and brain for IPM/CS. In systemic infection, CRB 529 and CRB 550 showed excellent efficacies against P. aeruginosa and S. aureus (MRSA) at a dose of 5 mg/kg. The PD$_{50s}$ were 0.80, 0.36 mg/kg for CRB 529 and CRB 550, respectively, and 3.22 mg/kg for IPM/CS against P. aeruginosa. The corresponding values against S. aureus (MRSA) were 76.0, 55.3 mg/kg for CRB 529 and CRB 550, respectively, and 146 mg/kg for IPM/CS. In local infection, the antibacterial activities of CRB 529 and CRB 550 were more effective than those of IPM/CS against intrarenal infection with E. coli and P. aeruginosa and also showed as effective as IPM/CS against respiratory tract infection with E. coli and P. aeruginosa at a dose of 5 mg/kg.

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The Bacterial Community Structure in Biofilms of the RABC Process for Swine Butchery Wastewater Treatment (돼지 도축폐수 처리를 위한 RABC 공정의 생물막 세균군집 구조)

  • Sung, Gi-Moon;Lee, Dong-Geun;Park, Seong-Joo
    • Korean Journal of Microbiology
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    • v.47 no.1
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    • pp.56-65
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    • 2011
  • Culture-independent microscopic observations and 16S rDNA analyses were applied to describe the bacterial community inherent to the biofilm structure of the RABC (Rotating Activated Bacillus Contactors) process for swine butchery wastewater treatment. The ratios of Gram-positive bacterial counts to total bacterial counts of the RABC process were significantly increased in the last aeration tank as well as returned sludge, while those of the existing A2O (Anaerobic-Anoxic-Oxic) process maintained constant from aeration tanks to returned sludge. Totally nine phyla were recovered by 16S rDNA analysis, two of which were major groups: the Proteobacteria (64.1%) and the Actinobacteria (18.4%). The third major group was the endospore-forming Firmicutes (5.4%). The remaining six minor groups are the Bacteroidetes (3.3%), the Chlorobi (2.2%), the Nitrospirae (1.1%), the Chlorofleix (1.1%), the Acidobacteria (1.1%), and the Fusobacteria (1.1%). The ratio of endospore-forming bacteria was 19.4%, which was composed of the members of the Firmicutes phylum (5.4%) and the Intrasporangiaceae family (14.0%) of the Actinobacteria phylum. Nitrifying and denitrifying related- and phosphorus accumulating related-sequences were composed of 6.5% and 5.4% of total community, respectively, these could mean the high capacity of the RABC process to remove odor compounds and reduce eutrophication by efficient removing inorganic nutrients.

Gene Transfer Optimization via E. coli-driven Conjugation in Nocardiopsis Strain Isolated via Genome Screening (유전체 스크리닝으로 선별된 Nocardiopsis 균주의 대장균 접합을 통한 유전자 도입전략 최적화)

  • Jeon, Ho-Geun;Lee, Mi-Jin;Kim, Hyun-Bum;Han, Kyu-Boem;Kim, Eung-Soo
    • Microbiology and Biotechnology Letters
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    • v.39 no.2
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    • pp.104-110
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    • 2011
  • Actinomycetes, Gram positive soil bacteria, are valuable microorganisms which produce useful secondary metabolites including antibiotics, antiparasitic substances, anti-cancer drugs, and immunosuppressants. Although a major family of actinomycetes, known as streptomycetes, has been intensively investigated at the molecular level for several decades, a potentially valuable and only recently isolated non-streptomycetes rare actinomycetes (NSRA) family has been poorly characterized due to lack of proper genetic manipulation systems. Here we report that a PCR-based genome screening strategy was performed with approximately 180 independently isolated actinomycetes strains to isolate potentially valuable NSRA strains. Thanks to this simple PCR-based genome screening strategy we were able to identify only seven NSRA strains, followed by 16S rRNA sequencing for confirmation. Through further bioassays, one potentially valuable NSRA strain (tentatively named Nocardiopsis species MMBL010) was identified which possessed both antifungal and antibacterial activities, along with the presence of polyketide synthase and non-ribosomal peptide synthase genes. Moreover, Nocardiopsis species MMBL010, which was intrinsically recalcitrant to genetic manipulation, was successfully transformed via E. coli-driven conjugation. These results suggest that PCR-based genome screening, followed by the establishment of an E. coli-driven conjugation system, is an efficient strategy to maximize potentially valuable compounds and their biosynthetic genes from NSRA strains isolated from various environments.

Effect of Environmental Conditions and Chemical Treatments on Seed Germination of Astilbe koreana (Kom.) Nakai (자생 숙은노루오줌의 종자발아에 미치는 환경조건과 화학적 처리의 영향)

  • Jang, Bo Kook;Cho, Ju Sung;Lee, Cheol Hee
    • Korean Journal of Plant Resources
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    • v.29 no.2
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    • pp.235-240
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    • 2016
  • Factors affecting germination of seeds in the forms of various environment and chemical compounds. The present study was aim to produced effective seed propagation method of Astilbe koreana (Kom.) Nakai which had expected high value for the cut flower, ornamental and pharmaceutical material. Seed width and length ranged 0.62, 2.22 ㎜, respectively, and weight of thousand seeds was 40.5 ㎎. As result of imbibition test, showed moisture content of fresh seed (2.57%) increased rapidly by water-soaking treatment under 24 hours, recording to maximum value of 29.8%, and expansion of the seed coat was observed. Seed germination was the best at 15℃ and light conditions (40.8%) among temperature and light conditions treated. Percent germination of seeds was improved under the low (15, 20℃) than high temperature (25, 30℃). In addition, the seed was not germinated at dark condition regardless of temperature. Seeds of A. koreana thus seemed that it had low temperature germinability conditions. To improve germination rate, seeds were submerged in various concentrations of growth regulators such as GA3 and kinetin, and minerals as KNO3 and KCl. As a results, KNO3 treatment, regardless of concentrations, promoted germination compared to control. Especially, percent of germination (77.8%), germination energy (96.1%), mean germination time (11.3 days) and T50 (6.5 days) were effectively improved by treatment of KNO3 20 mM.

Alkaloids from Beach Spider Lily (Hymenocallis littoralis) Induce Apoptosis of HepG-2 Cells by the Fas-signaling Pathway

  • Ji, Yu-Bin;Chen, Ning;Zhu, Hong-Wei;Ling, Na;Li, Wen-Lan;Song, Dong-Xue;Gao, Shi-Yong;Zhang, Wang-Cheng;Ma, Nan-Nan
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.21
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    • pp.9319-9325
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    • 2014
  • Alkaloids are the most extensively featured compounds of natural anti-tumor herbs, which have attracted much attention in pharmaceutical research. In our previous studies, a mixture of major three alkaloid components (5, 6-dihydrobicolorine, 7-deoxy-trans-dihydronarciclasine, littoraline) from Hymenocallis littoralis were extracted, analyzed and designated as AHL. In this paper, AHL extracts were added to human liver hepatocellular cells HepG-2, human gastric cancer cell SGC-7901, human breast adenocarcinoma cell MCF-7 and human umbilical vein endothelial cell EVC-304, to screen one or more AHL-sensitive tumor cell. Among these cells, HepG-2 was the most sensitive to AHL treatment, a very low dose ($0.8{\mu}g/ml$) significantly inhibiting proliferation. The non-tumor cell EVC-304, however, was not apparently affected. Effect of AHL on HepG-2 cells was then explored. We found that the AHL could cause HepG-2 cycle arrest at G2/M checkpoint, induce apoptosis, and interrupt polymerization of microtubules. In addition, expression of two cell cycle-regulated proteins, CyclinB1 and CDK1, was up-regulated upon AHL treatment. Up-regulation of the Fas, Fas ligand, Caspase-8 and Caspase-3 was observed as well, which might imply roles for the Fas/FsaL signaling pathway in the AHL-induced apoptosis of HepG-2 cells.

The Occurrences of Pharmaceutical and Personal Care Products (PPCPs) in Mankyung River, South Korea (만경강 수중에서 신체보초제품(PPCPS)의 잔류)

  • Kim, Joon-Woo;Kim, Jong-Gu;Jang, Hyo-Sang;Cho, Hyeon-Seo;Takao, Yuji;Arizono, Koji
    • Journal of Environmental Science International
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    • v.18 no.3
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    • pp.245-254
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    • 2009
  • In recent years, environmental pollution by phannaceuticals and personal care products (PPCPs) in the aquatic environment is of great concern worldwide. Recent studies have been reported to occur in a variety of environmental organisms such as surface, drinking and ground water, soils, sediments and hospitals. The purpose of this study was to evaluate the occurrence and environmental behavior of fourteen human PPCPs in surface waters of Mankyung River in South Korea. We were conducted to field survey for water quality and PPCPs analysis at November, 2006. PPCPs were analyzed by liquid chromatograph coupled with a tandem mass spectrometer (HPLC-MS/MS). The concentration of COD was measured to be 2.37$\sim$19.71 mg/L, which was belong to 4$\sim$5 grade in water quality criteria of lake. Station 2 that there is no pollution in upper stream, was appeared to lower concentration. The concentration of TN and TP, that is cause matter of eutrophication, were found to be 7.78$\sim$35.42 mg/L and 0.08$\sim$0.95 mg/L, respectively, which were exceeding 5 grade in Lake water quality criteria. The 11 kind of PPCPs compounds except levofloxacin and triclosan were detected to Mankyung river. PPCPs concentrations of STP(Sewer Treatment Plant) effluents and aquatic environment in Mankyung river have been detected in the range from dozens of ng/L to hundreds of ${\mu}g/L$ that by order of atenolol, carbamazepine, propranolol, Ibuprofen, erythromycin, ifenprodil, clarithromycin, mefenamic acid, fluconazole, indomethacin, disopyramide. PPCPs concentration of Station 1 and 5, which was influenced by Jeonju STP and Wanju STP, was detected high values. Station 2 that there is no pollution, showed lower values. Station 3 which joined Gosan stream and Jeonju stream and station 4 which influenced by stock wastewater was detected to low values.

Phenolic Compound Content and Antioxidant Activity of Citrus Peels (감귤 과피의 페놀성 화합물 함량과 항산화 활성)

  • Hwang, Joon-Ho;Park, Kyeong-Yeol;Oh, You-Sung;Lim, Sang-Bin
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.42 no.2
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    • pp.153-160
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    • 2013
  • The peel from seven types of citrus was extracted with 80% methanol, and their phenolic compound content, oxygen radical absorbance capacity (ORAC), inhibitory activities of nitric oxide (NO), and reactive oxygen species (ROS) production induced by LPS and t-BHP in LPS-activated RAW 264.7 cells were measured. Total phenolic content was high in Yungkyool, Cheonhyehyang, and Jinkyool (30.6, 30.2, and 28.2 mg GAE/g, respectively), while total flavonoid content was high in Yungkyool and Jinkyool (30.3 and 25.5 mg RE/g, respectively). ORAC was the highest at 1,076 mM TE/g in Yungkyool, followed by Cheonhyehyang (1,012), Jinkyool (984), and Hallabong (914). High inhibitory activity against NO production was shown in Cheonhyehyang, Yungkyool, and Jinkyool with $IC_{50}$ values of 215.3, 259.2, and 328.9 ${\mu}g/mL$, respectively. LPS-induced ROS production was inhibited by 16.4% and 12.8% in Hallabong and Jinkyool, while t-BHP-induced ROS production was inhibited by 28.7%, 26.1%, and 26.6% in Jinkyool, Hallabong, and Cheonhyehyang, respectively. Correlation coefficients between total phenolic, total flavonoid content, and ORAC were 0.884 and 0.855. Inhibitory activity against NO production showed higher correlation with total phenolic content than total flavonoid content. It was concluded that citrus peels had potent antioxidant activities and could be used as natural antioxidants in the food and pharmaceutical industries.