• 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.

• Analytical Science and Technology
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• v.23 no.6
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• pp.544-550
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• 2010

Mistaking pink colored thermal oil for grape wine, a victim drank the oil to death which was analyzed to contain 39% of ethylene glycol. Thermal oil could be used for heat transfer to prevent the malfunction due to the high pressure in the boiler operated at high temperature when using water. Main component of thermal oil is known to be mineral oil or ethylene glycol. From the blood and other tissue of the victim from autopsy, ethylene glycol and its metabolite were simultaneously analyzed by GC/MS after extraction under acidic condition with acetonitrile followed by derivatization with BSTFA. About 0.2 g of the specimens were pretreated with 50 uL of 0.5 M HCl solution to keep acidic condition, then dehydrated with anhydrous sodium sulfate followed by concentration under nitrogen stream. Ethylene glycol and glycolic acid concentration in blood was measured to be $2,755\;{\mu}g/mL$ and $174\;{\mu}g/mL$ respectively. In other specimen, the concentration of ethylene glycol and glycolic acid was $860\;{\mu}g/g\sim1,290\;{\mu}g/g$ and $93\;{\mu}g/g\sim134\;{\mu}g/g$. Especially, crystal appeared in kidney which was supposed xalate from the metabolite of ethylene glycol.

• Proceedings of the Korean Vacuum Society Conference
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• 2016.02a
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• pp.378.1-378.1
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• 2016

나노바이오연구분야에서 ToF-SIMS를 이용하여 lipid와 metabolite같은 저 분자의 생체물질을 측정하는데 널리 이용되어 왔다. 최근에는 고 분자량의 생체물질을 측정하기 위해서 C60, water cluster, argon cluster등의 다양한 종류의 클러스터 이온빔들이 개발되어 왔다. [1,2] 하지만 tissue샘플을 클러스터 이온빔을 이용하여 분석한 결과에서도 m/z 1500이상의 고분자를 측정한 결과는 거의 없다. 바이오샘플의 charging을 상쇄하기위해 low energy electron beam (~20 eV)을 사용하는데, low energy electron beam이 샘플에 damage를 주기 때문이다. [3] 본 연구에서는 electron fluence (electrons/cm2)가 증가함에 따라 PC(16:0/18:1(9Z)와 Ganglioside GM1의 intensity가 감소함을 알았고, low energy electron beam에 의해 생체 물질이 damage를 받을 수 있음을 확인하였다. 따라서 tissue 샘플을 SUS기판에 샘플링하고 Ar-GCIB를 이용하면 charging없이 tissue imaging을 성공적으로 수행할 수 있고, m/z 2000이상의 고 분자량의 생체물질을 측정할 수 있음을 확인하였다.

• Toxicological Research
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• v.11 no.2
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• pp.289-294
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• 1995

This study was designed to observe the effect of tohiene pretreatment on leukocyte variation in whole blood and the oxygen free radical generating, scavenging enzyme activities in neutrophil of bacteria infected rats. Toluene was administered 7 times intraperitoneally at levels of 9.45 mM/kg body weight to the rats and then infected with S. aureus $2\times10^7$ cfu/ml. The toluene treated-rats showed the significantly decreased numbers of lymphocyte and monocytes, but the similiar numbers of neutrophils with the control. Furthermore the increased neutrophils in blood of bacteria infected rats were reduced by the toluene pretreatment. Concomitantly the increased activities of xanthine oxidase and superoxide dismutase in neutrophil of bacteria infected rats were also decreased by the toluene pretreatment. On the other hand, injection of benzaldehyde to rats also led to similiar results in the count of leukocytes, xanthine oxidase and superoxide dismutase activities of neutrophil with those of toluene treated rats. These data suggest that toluene and its intermediate metabolite, benzaldehyde influence on the phagocytosis and defence mechanism of neutrophil.

• The Korean Journal of Pesticide Science
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• v.3 no.2
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• pp.37-46
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• 1999

In order to ascertain the safety of the systemic insecticide carbofuran-treated crops, samples of garlic, peanut and potato were collected randomly from markets located in the main producing areas and analyzed for the residue of carbofuran and its main metabolite, 3-hydroxycarbofuran. The in vitro metabolism of carbofuran in phosphate buffer extracts of the crops was investigated. Two (M-12 and M-16) out of 20 mature garlic samples contained 0.13 and 0.07 mg/kg of carbohran, respectively, showing a detection incidence of 10%. The residue levels were less than the maximum residue limit (0.5 ppm) set by Korean Food and Drug Administration. Only one sample of mature garlic (M-12) out of 20 contained 0.13 mg/kg of 3-hydroxycarbofuran. The residues of carbofuran and 3-hydroxycarbofuran in the immature garlic, peanut and potato samples were less than the detection limits, 0.02 mg/kg for carbofuran and 0.06 mg/kg for 3-hydroxycarbofuran. The application of carbofuran to the fields of garlic, peanut and potato would be safe, considering that the estimated maximum acceptable daily intake of carbofuran from garlic was 0.0013 mg which is 0.24% of the maximum acceptable daily intake (0.55 mg). Carbofuran was hydrolyzed in vitro mainly to carbofuran phenol (m/z 164) in the respective phosphate buffer extracts of the three crops in contrast to the major oxidative metabolism in situ. The amount of the metabolite increased with the incubation time.

• Archives of Pharmacal Research
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• v.25 no.5
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• pp.664-668
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• 2002

KR-31543,(2S,3R,4S)-6-amino-4-[N-(4-chlorophenyl)-N-(2-methyl-2H-tetrazol-5-ylmethyl)amino]-3,4-dihydro-2-dimethoxymethyl-3-hydroxy-2-methyl-2H-1-benzopyran is a new neuroprotetive agent for ischemia-reperfusion damage. The in vitro and in vivo metabolism of KR-31543 in rats has been studied by LC-electrospray mass spectrometry. Rat liver microsomal incubation of KR-31543 in the presence of NADPH resulted in the formation of a metabolite M1. M1 was identified as N-(4-chlorophenyl)-N-(2-methyl-2H-tetrazol-5-ylmethyl)amine on the basis of LC-MS/MS analysis with the synthesized authentic standard. Rat CYP3A1 and 3A2 are the major CYP isozymes involved in the formation of M1.

• The Korean Journal of Nuclear Medicine
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• v.37 no.6
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• pp.402-417
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• 2003

Purpose: To evaluate the use of monoclonal antibody (MoAb) as a carrier of the receptor-binding ligand the receptor mediated uptake into liver and subsequent metabolism of $^{111}In-labeled$ galactosylated MoAb-chelator conjugates were investigated and compared with those of $^{111}In$ labeled MoAb. Materials and Methods : T101 MoAb, $IgG_2$ against human lymphocytic leukemic cell, conjugated with cyclic DTPA dianhydride (DTPA) or 2-p-isothiocyanatobenzyl-6-methyl-DTPA (1B4M) was galactosylated with 2-imino-2-methoxyethyl-1-thio-${\beta}$-D-galactose and then radiolabeled with $^{111}In$. Biodistribution and metabolism study was peformed with two $^{111}In-conjugates$ in mice and rats. Results: $^{111}In-labeled$ T101 and its galactosylated conjugates were taken to the liver by the time, mostly within 10 min. However DTPA conjugate was retained longer in the liver than the 1B4M conjugate (55% vs 20% of injected dose at 44 hr). During this time, the radiornetabolite of DTPA conjugate was excreted similarly into urine (24%) and feces (17%). The radiometabolite of 1B4M was excreted primarily into feces (68%) rather than urine (8%). Size exclusion HPLC analysis of the bile and supernatant of liver homogenate showed two peaks the first (35%) with the retention time (Rt) identical to IgG and the second (65%) with Rt similar to free $^{111}In$ at 3 hr post-injection for the 1B4M conjugate, indicating that the metabolite is rapidly excreted through the biliary system. in contrast to DTPA conjugate, the small $^{111}In-DTPA-like$ metabolite was the major radioindium component (90%) in the liver homogenate as early as 3 hour post-injection, but the cumulative radioindium activity in feces was only 17% at 44 hour, indicating that the metabolite from DTPA conjugate does not clear readily through the biliary tract. Conclusion: The galactosylation of the MoAb conjugates resulted in higher hepatocyte uptake and enhanced metabolism, compared to those without galactosylation. Metabolism of the MoAb-conjugates is different between compounds radiolabled with different chelators due to different characteristics of radiometabolites generated in the liver.

• Investigative Magnetic Resonance Imaging
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• v.13 no.2
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• pp.117-126
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• 2009

Purpose : A numerical method of designing a multiple quantum filter (MQF) is presented for the optimum detection of myo-inositol (mI), an important brain metabolite, by using in vivo proton nuclear magnetic resonance spectroscopy ($^1$-HMRS). Materials and Methods : Starting from the characterization of the metabolite, the filter design includes the optimization of the sequence parameters such as the two echo times (TEs), the mixing time (TM), and the flip angle and offset frequency of the 3rd $90^{\circ}$ pulse which converts multiple quantum coherences (MQCs) back into single quantum coherences (SQCs). The optimized filter was then tested both in phantom and in human brains. Results : The results demonstrate that the proposed MQF can improve the signal-to-background ratio of the target metabolite by a factor of more than three by effectively suppressing the signal from the background metabolites. Conclusion : By incorporating a numerical method into the design of MQFs in $^1$-HMRS the spectral integrity of a target metabolite, in particular, with a complicated spin system can be substantially enhanced.

• Journal of Ginseng Research
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• v.43 no.1
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• pp.154-160
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• 2019

Background: Compound K (CK) is an active metabolite of ginseng saponin, ginsenoside Rb1, that has been shown to have ameliorative properties in various diseases. However, its role in inflammation and the underlying mechanisms are poorly understood. In this report, the antiinflammatory role of CK was investigated in macrophage-like cells. Methods: The CK-mediated antiinflammatory mechanism was explored in RAW264.7 and HEK293 cells that were activated by lipopolysaccharide (LPS) or exhibited overexpression of known activation proteins. The mRNA levels of inflammatory genes and the activation levels of target proteins were identified by quantitative and semiquantitative reverse transcription polymerase chain reaction and Western blot analysis. Results: CK significantly inhibited the mRNA expression of inducible nitric oxide synthase and tumor necrosis factor-${\alpha}$ and morphological changes in LPS-activated RAW264.7 cells under noncytotoxic concentrations. CK downregulated the phosphorylation of AKT1, but not AKT2, in LPS-activated RAW264.7 cells. Similarly, CK reduced the AKT1 overexpression-induced expression of aldehyde oxidase 1, interleukin-$1{\beta}$, interferon-${\beta}$, and tumor necrosis factor-${\alpha}$ in a dose-dependent manner. Conclusion: Our results suggest that CK plays an antiinflammatory role during macrophage-mediated inflammatory actions by specifically targeting the AKT1-mediated signaling pathway.

• Journal of Ginseng Research
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• v.36 no.1
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• pp.55-60
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• 2012

In a previous report, we demonstrated that ginsenoside Rc, one of major ginsenosides from Panax ginseng, enhances ${\gamma}$-aminobutyric acid (GABA) $receptor_A$ ($GABA_A$)-mediated ion channel currents. However, little is known about the effects of ginsenoside metabolites on $GABA_A$ receptor channel activity. The present study investigated the effects of ginsenoside metabolites on human recombinant $GABA_A$ receptor (${\alpha}_1{\beta}_1{\gamma}_{2s}$) channel activity expressed in Xenopus oocytes using a two-electrode voltage clamp technique. M4, a metabolite of protopanaxatriol ginsenosides, more potently inhibited the GABA-induced inward peak current ($I_{GABA}$) than protopanaxadiol (PPD), a metabolite of PPD ginsenosides. The effect of M4 and PPD on $I_{GABA}$ was both concentration-dependent and reversible. The half-inhibitory concentration ($IC_{50}$) values of M4 and PPD were 17.1${\pm}$2.2 and 23.1${\pm}$8.6 ${\mu}M$, respectively. The inhibition of $I_{GABA}$ by M4 and PPD was voltage-independent and non-competitive. This study implies that the regulation of $GABA_A$ receptor channel activity by ginsenoside metabolites differs from that of ginsenosides.