• The Korean Journal of Pesticide Science
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• v.11 no.2
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• pp.87-94
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• 2007

Pyrethroid insecticide have widely been used for agricultural sector and residential environments. To assess the exposure of insecticide which is absorbed through skin the analysis of urinary metabolite is essential. At present, the urinary 3-PBA was analyzed using liquid-phase extraction. But LPE have many limitations, such as long pre-treatment time and low recovery. So, this study was conducted to determine the optimum conditions for analysing 3-PBA in urine using solid phase extraction. Furthermore, this study intend to investigate the relation of concentrations of pyrethroid, deltamethrin in air and 3-PBA in urine. The optimum condition for hydrolysis was found to be done with hydrochloric acid for one hour. The recovery rates of 3-PBA were $84.6%{\pm}1.2%$, $54.8{\pm}0.9%$, $99.8{\pm}1.2%$ with XAD-2, XAD-7, XAD-16 using as the aborbents and acetone as eluents respectively. But acetonitrle and methanol gave low recovery rate and methyl cellosolve could not elute the compound. The amount of acetone for elution were 6mL, 9mL, 3mL for XAD-2, XAD-7, XAD-16 as absorbents respectively. The non-absorbed rates was $0.8{\pm}0.5%$, and $0.7{\pm}0.3%$ under XAD-16, mesh size 140-200, amount of resin 1.4g and the flow rate of eluent was 0.1mL/min. In the concentration process, we obtained 11 times higher concentration of material. The amounts of urinary 3-PBA were. The LODs of 3-PBA and deltamethrin were 0.004 mg/L, 0.038 mg/L, respectively. The further research of minute monitoring which include spray pattern, environmental condition is needed And more research about the relation between total pyrethroid exposure and urinary various metabolite are also necessary.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2018.04a
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• pp.14-14
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• 2018

This Camptotheca acuminata Decne. (CA), belonging to Nyssaceae, is a deciduous tree. and has been used as Traditional Chinese medicine since ancient times. The CA produces camptothecin a natural indole alkaloid, and reported to have anti-cancer effects. But the studies on biological activities of CA leaves are insufficient. Therefore, this study confirmed various biological activities such as antioxidant, antidiabetic, anticancer, antiinflammatory and metabolism analysis by HPLC-MS/MS of CA leaves. The $RC_{50}$ values of DPPH radical scavenging activity of ethyl acetate fraction, n-Butanol fraction, methanol extraction, water fraction and n-Hexane fraction were $12.23{\pm}0.01$, $15.93{\pm}0.42$, $55.12{\pm}0.45$, $56.29{\pm}4.15$ and $427.29{\pm}6.13ug/mL$, respectively. The $IC_{50}$ values of ${\alpha}$-glucosidase inhibitory activity of ethyl acetate fraction, n-Butanol fraction, methanol extraction, n-Hexane fraction and water fraction were $24.29{\pm}0.14$, $47.86{\pm}0.45$, $54.23{\pm}1.21$ $466.76{\pm}2.21$ and $623.91{\pm}9.67ug/mL$, respectively. The nitric oxide release activity of n-Hexane fraction, methanol extraction, ethyl acetate fraction, water fraction and n-Butanol fraction were $31.49{\pm}5.74$, $29.79{\pm}0.71$, $26.89{\pm}0.71$, $8.24{\pm}5.83$ and $7.75{\pm}4.08%$ at 25 ug/mL, respectively. The anti-cancer activity of n-Hexane fraction, methanol extraction, ethyl acetate fraction, water fraction and n-Butanol fraction were $31.49{\pm}5.74$, $29.79{\pm}0.71$, $26.89{\pm}0.71$, $8.24{\pm}5.83$ and $7.75{\pm}4.08%$ at 25 ug/mL, respectively. The ethyl acetate fraction activities showed higher biological activities than other fractions. Thus, Additional studies were conducted using ethyl acetate fraction. Metabolite analysis was performed using a LCMS-8040 triple quadrupole mass spectrometer. As a result, Five compounds (1-5) were identified in the ethyl acetate fraction of the CA leave. The identification of these compounds was generated by the analysis of fragmentation methods of the negative and positive ion modes. Five compounds were identified as gallic acid (1), chlorogenic acid (2), isoquercetin (3), astragalin (4) and camptothecin (5). These results suggest that the CA leave can be used for functional materials.

• Journal of Pharmaceutical Investigation
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• v.22 no.3
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• pp.197-204
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• 1992

A gas chromatographic method using nitrogen phosphorous selective detection was developed for simultaneous determination of haloperidol and its metabolite, reduced haloperidol, in human plasma. Combelen was used as internal standard, The method involved extraction and trimethylsilylation followed by the injection of $2-4\;{\mu}l$ of benzene layer, which was used to dissolve the trimethylsilylated derivatives of haloperidol and reduced haloperidol, onto SE-54 column [5% phenyl methyl silica fused capillary column, $16m{\times}0.22\;mm$ $(I.D.){\times}0.33\;{\mu}m$ (coated thickness)]. The temperature of column oven was programmed from $200^{\circ}C\;to\;300^{\circ}C$ at the increase rate of $10^{\circ}C/min and also the temperatures of injector and detector were set at $300^{\circ}C$. Helium was used as carrier gas and its flow rate was maintained at 30 ml/min. The detection was conducted with nitrogen phosphorous selective detector. The retention times for combelen, reduced haloperidol and haloperidol were found to be 9.14, 9.75 and 9.99 min, respectively. The detection limits for haloperidol and reduced haloperidol in human plasma were both 0.2 ng/ml. The coefficients of variation of the intra-assay were generally low (below 9.8%). The mean absolute recoveries of added haloperidol and reduced haloperidol from plasma were 72% and 84%, respectively. No interferences from endogenous substances were found.

• Archives of Pharmacal Research
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• v.24 no.3
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• pp.207-210
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• 2001

A fully automated high performance liquid chromatography with column-switching was developed for the simultaneous determination of KR60436, a new reversible proton pump inhibitor, and its active metabolite O-Demethyl-KR60436 from rat plasma samples. Plasma sample (50$\mu$l) was directly introduced onto a Capcell Pak MF Ph-1 column ($10{\times}4$ mm I.D.) where primary separation was occurred to remove proteins and concentrate target Substances Using acetonitrile-Potassium Phosphate (PH 7, 0.1 M) (2 : 8, v/v). The drug molecules eluted from MF Ph-1 column were focused in an intermediate column ($10{\times}2$ I.D.) by the valve switching step. The substances enriched in intermediate column were eluted and separated on a Vydac 218MR53 column ($250{\times}3.2$ I.D.) using acetonitrilepotassium phosphate (pH 7, 0.02 M) (47:53, v/v) at a flow rate of 0.5 ml/min when the valve status was switched back to A position. The method showed excellent sensitivity (detection limit of 2 ng/ml) with small volume of samples ($50{\mu}$l), good precision and accuracy, and speed (total analysis time 24 min) without any loss in chromatographic efficiency. The response was linear ($r^2{\geq}0.797$) over the concentration range of 5-500 ng/ml.

• Archives of Pharmacal Research
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• v.28 no.10
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• pp.1196-1202
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• 2005

Omeprazole (OMP) is a proton pump inhibitor used as an oral treatment for acid-related gastrointestinal disorders. In the liver, it is primarily metabolized by cytochrome P-450 (CYP450) isoenzymes such as CYP2C19 and CYP3A4. 5-Hyroxyomeprazole (5-OHOMP) and omeprazole sulfone (OMP-SFN) are the two major metabolites of OMP in human. Cimetidine (CMT) inhibits the breakdown of drugs metabolized by CYP450 and reduces, the clearance of coad-ministered drug resulted from both the CMT binding to CYP450 and the decreased hepatic blood flow due to CMT. Phenobarbital (PB) induces drug metabolism in laboratory animals and human. PB induction mainly involves mammalian CYP forms in gene families 2B and 3A. PB has been widely used as a prototype inducer for biochemical investigations of drug metabolism and the enzymes catalyzing this metabolism, as well as for genetic, pharmacological, and toxicological investigations. In order to investigate the influence of CMT and PB on the metabolite kinetics of OMP, we intravenously administered OMP (30 mg/kg) to rats intraperitoneally pretreated with normal saline (5 mL/kg), CMT (100 mg/kg) or PB (75 mg/kg) once a day for four days, and compared the pharmacokinetic parameters of OMP. The systemic clearance ($CL_{t}$) of OMP was significantly (p<0.05) decreased in CMT-pretreated rats and significantly (p<0.05) increased in PB-pretreated rats. These results indicate that CMT inhibits the OMP metabolism due to both decreased hepatic blood flow and inhibited enzyme activity of CYP2C19 and 3A4 and that PB increases the OMP metabolism due to stimulation of the liver blood flow and/or bile flow, due not to induction of the enzyme activity of CYP3A4.

• Korean Journal of Environmental Biology
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• v.23 no.4
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• pp.405-408
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• 2005

To induce the enhanced mutants of dinitroaniline herbicide pendimethalin degrading bacterium, Bacillus sp. MS202 was irradiated with gamma radiation at the dose of $LD_{99}$ (3.35 kGy). Three enhanced mutants (MS202m7, MS202m14, MS202m18) were isolated from the candidates by the generation - isolation method. Clear zone formation and the GC analysis confirmed that the degrading activity of each enhanced mutant (MS202m7, MS202m14, MS202m18), the formation of pendimethalin metabolite, increased by $11\%,\;45\%,\;and\;32\%$ than a wild type, respectively. It suggested that these mutants induced by gamma radiation could be useful for the application of pesticide degradation.

• Journal of Applied Biological Chemistry
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• v.62 no.1
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• pp.81-86
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• 2019

A yellow resin (gamboge) from Garcinia hanburyi has been widely used as folk medicine due to its antibacterial and antitumor activities. We isolated four ${\alpha}$-glucosidase inhibitory compounds from the methanol extract of gamboge. The compounds (1-4) were identified as gambogoic acid (1), moreollic acid (2), gambogic acid (3), and 10-methoxygambogenic acid (4), respectively through spectroscopic data including 2D-NMR and HREIMS. All compounds were examined in the enzyme inhibition assay against ${\alpha}$-glucosidase to identify their inhibitory potencies and kinetic behavior. All compounds (1-4) showed enzyme inhibition against ${\alpha}$-glucosidase, but the activity was significantly affected by the methoxy group on C-10 of ring A and pentenyl pyran moiety of ring D. For example, compound 1 ($IC_{50}=41.4{\mu}M$) bearing pyran ring eight times effective that 4 ($IC_{50}=350.6{\mu}M$) having geranyl group itself. Most active compound was found out to be gambogoic acid (1) which was analyzed most abundant metabolite in gamboge by LC-ESI-MS/MS. In kinetic study, compounds 1 and 2 were proved as noncompetitive inhibitors.

• Natural Product Sciences
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• v.21 no.4
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• pp.282-288
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• 2015

Viriditoxin is a fungal metabolite isolated from Paecilomyces variotii, which was derived from the giant jellyfish Nemopilema nomurai. Viriditoxin was reported to inhibit polymerization of FtsZ, which is a key protein for bacterial cell division and a structural homologue of eukaryotic tubulin. Both tubulin and FtsZ contain a GTP-binding domain, have GTPase activity, assemble into protofilaments, two-dimensional sheets, and protofilament rings, and share substantial structural identities. Accordingly, we hypothesized that viriditoxin may inhibit eukaryotic cell division by inhibiting tubulin polymerization as in the case of bacterial FtsZ inhibition. Docking simulation of viriditoxin to ${\beta}-tubulin$ indicated that it binds to the paclitaxel-binding domain and makes hydrogen bonds with Thr276 and Gly370 in the same manner as paclitaxel. Viriditoxin suppressed growth of A549 human lung cancer cells, and inhibited cell division with G2/M cell cycle arrest, leading to apoptotic cell death.

• Mass Spectrometry Letters
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• v.5 no.4
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• pp.104-109
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• 2014

Nonmedical use of prescription stimulants such as methylphenidate (MPH) and amphetamine (AP) by normal persons has been increased to improve cognitive functions. Due to high potential for their abuse, reliable analytical methods were required to detect these prescription stimulants in biological samples. A direct injection liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed and implemented for simultaneous determination of MPH, AP and their metabolites ritalinic acid (RA) and 4-hydroxyamphetamine (HAP) in human urine. Urine sample was centrifuged and the upper layer ($100{\mu}L$) was mixed with $800{\mu}L$ of distilled water and $100{\mu}L$ of internal standards ($0.2{\mu}g/mL$ in methanol). The mixture was then directly injected into the LC-MS/MS system. The mobile phase was composed of 0.2% formic acid in distilled water (A) and acetonitrile (B). Chromatographic separation was performed by using a Capcell Pak MG-II C18 ($150mm{\times}2.0mm$ i.d., $5{\mu}m$, Shiseido) column and all analytes were eluted within 5 min. Linear least-squares regression with a 1/x weighting factor was used to generate a calibration curve and the assay was linear from 20 to 1500 ng/mL (HAP), 40-3000 ng/mL (AP and RA) and 2-150 ng/mL (MPH). The intra- and inter-day precisions were within 16.4%. The intra- and inter-day accuracies ranged from -15.6% to 10.8%. The limits of detection for all the analytes were less than 4.7 ng/mL. The suitability of the method was examined by analyzing urine samples from drug abusers.

• YAKHAK HOEJI
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• v.51 no.2
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• pp.133-139
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• 2007

A simple and sensitive HPLC-MS method for quantitation of 10${\alpha}$-methoxy-9,10-dihydrolysergol (MDL), the main metabolite of nicergoline, in human plasma was developed and the bioavailability parameters of MDL was assessed in Korean healthy male volunteers. Clomipramine was used as an internal standard. MDL and internal standard in plasma sample were extracted using ethyl acetate. A centrifuged upper layer was then evaporated and reconstituted with mobile phase of 10 mM ammonium acetate-acetonitrile (10 : 90, v/v). The reconstituted samples were injected into a Zorbax SB-C8 column (2.1${\times}$150 mm,5 ${\mu}$m) at a flow-rate of 0.3 ml/min. Using MS with selected ion monitoring (SIM) mode, MDL and clomipramine were detected without severe interference from human plasma matrix. MDL produced a protonated molecular ion ([M+H]$^+$) at m/z 287. Internal standard produced a protonated molecular ion ([M+H]$^+$) at m/z 315. A linear relationship for MDL was found in the range of 2.5${\sim}$100 ng/ml. The lower limit of quantitation (LLOQ) was 2.5 ng/ml with acceptable precision and accuracy. The intra- and inter-day validation for all coefficients of variation (R.S.D.%) were found less than 15%. Main pharmacokinetic parameters of 30 mg of nicergoline were revealed as follows: AUC$_t$ 321.1${\pm}$64.5 ng${\cdot}$hr/ml, C$_{max}$, 51.2${\pm}$25.3 ng/ml, T$_{max}$ 3.6${\pm}$1.5 hr, K$_{el}$ 0.12${\pm}$0.07 hr$^{-1}$ and t$_{1/2}$ 7.6${\pm}$3.4 hr. Inter subject variations and race differences were shown in comparison with the published data in the literature.