• Journal of Ginseng Research
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• v.43 no.4
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• pp.539-549
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• 2019

Background: 20(S)-Protopanaxadiol (PPD), the aglycone part of 20(S)-protopanaxadiol ginsenosides, possesses antidepressant activity among many other pharmacological activities. It is currently undergoing clinical trial in China as an antidepressant. Methods: In this study, an ultra-performance liquid chromatography coupled with triple quadrupole time-of-flight mass tandem mass spectrometry method was established to identify the metabolites of PPD in human plasma and urine following oral administration in phase IIa clinical trial. Results: A total of 40 metabolites in human plasma and urine were identified using this method. Four metabolites identified were isolated from rat feces, and two of them were analyzed by NMR to elucidate the exact structures. The structures of isolated compounds were confirmed as (20S,24S)-epoxydammarane-12,23,25-triol-3-one and (20S,24S)-epoxydammarane-3,12,23,25-tetrol. Both compounds were found as metabolites in human for the first time. Upon comparing our findings with the findings of the in vitro study of PPD metabolism in human liver microsomes and human hepatocytes, metabolites with m/z 475.3783 and phase II metabolites were not found in our study whereas metabolites with m/z 505.3530, 523.3641, and 525.3788 were exclusively detected in our experiments. Conclusion: The metabolites identified using ultra-performance liquid chromatography coupled with triple quadrupole time-of-flight mass spectrometry in our study were mostly hydroxylated metabolites. This indicated that PPD was metabolized in human body mainly through phase I hepatic metabolism. The main metabolites are in 20,24-oxide form with multiple hydroxylation sites. Finally, the metabolic pathways of PPD in vivo (human) were proposed based on structural analysis.

• Toxicological Research
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• v.12 no.1
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• pp.9-15
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• 1996

We studied the effects of a single, combined and mixed exposure of benzene, toluene and xylene on the activities of rat liver microsomal AHH, ADH and ALDH, and the excretion of their metabolites in urine. The AHH activities of the rats treated in combination and mixture were slightly higher and/or similar to those rats treated with single solvent, while the reverse effects were observed for ADH and ALDH. Similar effects were observed when the metabolites were examined in urine (p < 0.01). These results suggest that each solvent might interJkre the induction and action of ADH and ALDH, and decrease the excretion of their metabolites into urine.

• Safety and Health at Work
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• v.2 no.1
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• pp.57-64
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• 2011

Objectives: Although phthalates like dibutyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP) are commonly used as plasticizers and their metabolites are especially suspected of reproductive toxicity, little is known about occupational exposure to those phthalates. The aim of this study was to assess the utility of measuring the metabolite concentrations of DBP and DEHP in serum and urine samples as an indicator of occupational exposure to those phthalates. Methods: Phthalate metabolites were analyzed by using column-switching high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS). Results: We detected phthalate metabolites in serum and urine matrices at approximately 10-fold lower than the limit of detection of those metabolites in the same matrix by LC-MS/MS without column switching, which was sufficient to evaluate concentrations of phthalate metabolites for industrial workers and the general population. Conclusion: The accuracy and precision of the analytical method indicate that urinary metabolite determination can be a more acceptable biomarker for studying phthalate exposure and adverse health outcomes.

• Bulletin of the Korean Chemical Society
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• v.30 no.7
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• pp.1489-1496
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• 2009

This study was done for the determination and excretion profile of adrenosterone and its metabolites in human urine using both liquid chromatography with atmospheric pressure chemical ionization mass spectrometry and gas chromatography with mass spectrometry. Adrenosterone and its two metabolites were detected in human urine after administration a healthy volunteer with 75 mg of adrenosterone. We found that adrenosterone-M1 ($C_{19}H_{26}O_3$) was a reduction and adrenosterone-M2 ($C_{19}H_{26}O_4$) was a hydroxylation at C-ring, which did not know the exact position of the C-ring. The adrenosterone parent was detected by GC/TOF-MS, but not detected by LC/APCI/MS because of low intensity. Adrenosterone and its two metabolites were excreted as their glucuronided fractions. The recovery of this method ranged from 100.7 to 118.4% and the reproducibility and accuracy test were 85.5 to 112.0% and 1.1 to 8.4%, respectively. The excretion studies showed that adrenosterone and its metabolites were detectable in human urine during a 48 h period after oral administration, with maximum level of excretion at 4.1 h. The glucuro-/sulfaconjugated ratio of adrenosterone, M1 and M2 was 0.73 ${\pm}$ 0.03, 0.96 ${\pm}$ 0.06 and 0.89 ${\pm}$ 0.03 (n = 6), respectively. The amounts of adrenosterone excreted in urine were 14.75 ng for 48 h. Also, the maximum level of androsterone and 11$\beta$-hydroxy androsterone, which were endogenous steroids, were reached 4.1 h after the oral administration of adrenosterone.

• Environmental Analysis Health and Toxicology
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• v.29
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• pp.18.1-18.9
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• 2014

Objectives The purpose of this study was to determine a separation method for each arsenic metabolite in urine by using a high performance liquid chromatography (HPLC)-inductively coupled plasma-mass spectrometer (ICP-MS). Methods Separation of the arsenic metabolites was conducted in urine by using a polymeric anion-exchange (Hamilton PRP X-100, $4.6mm{\times}150mm$, $5{\mu}m$) column on Agilent Technologies 1260 Infinity LC system coupled to Agilent Technologies 7700 series ICP/MS equipment using argon as the plasma gas. Results All five important arsenic metabolites in urine were separated within 16 minutes in the order of arsenobetaine, arsenite, dimethylarsinate, monomethylarsonate and arsenate with detection limits ranging from 0.15 to $0.27{\mu}g/L$ ($40{\mu}L$ injection). We used G-EQUAS No. 52, the German external quality assessment scheme and standard reference material 2669, National Institute of Standard and Technology, to validate our analyses. Conclusions The method for separation of arsenic metabolites in urine was established by using HPLC-ICP-MS. This method contributes to the evaluation of arsenic exposure, health effect assessment and other bio-monitoring studies for arsenic exposure in South Korea.

• YAKHAK HOEJI
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• v.44 no.5
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• pp.384-390
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• 2000

Metabolism study of the dye, benzidine, was performed by gas chromatography-mass selective detector (GC/MSD) in the urine of rats orally administered 100 mg/kg benzidine. Urine samples were collected in metabolic cages for 0-24, 24-48, and 48-72 hrs. Ten ml of the urine was extracted with XAD-2 resin and the XAD-2 column was eluted with methanol. After evaporation, benzidine and its metabolites were extracted with diethyl ether (for non-conjugated fraction). For conjugated metabolites, $\beta$-glucu-ronidase was added to the aqueous layer that was incubated for 1 hr at 5$0^{\circ}C$ and the aqueous layer was extracted as in non-conjugated fraction. Aliquot of trimethylsilylated derivatives was applied to the GC/MSD. The mutagenicity of benzidine and its acetylated metabolites was tested by histidine/reversion assay. Five metabolites observed and confirmed either by electron impact and chemical ionization modes of the GC/MSD, or authentic compounds were monoacetyl-, diacetyl-, hydroxyacetyl-, hydroxydiacetyl-, and hydroxy-benzidine. Monoacetyl-benzidine was more potent than benzidine in histidine/reversion assay. This data indicates that monoacetylation of benzidine may be one of the metabolites produced in metabolic activation process.

• Journal of Veterinary Science
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• v.21 no.2
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• pp.23.1-23.10
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• 2020

The identification of biomarkers that distinguish diseased from healthy individuals is of great interest in human and veterinary fields. In this research area, a metabolomic approach and its related statistical analyses can be useful for biomarker determination and allow non-invasive discrimination of healthy volunteers from breast cancer patients. In this study, we focused on the most common canine neoplasm, mammary gland tumor, and herein, we describe a simple method using ultra-high-performance liquid chromatography to determine the levels of tyrosine and its metabolites (epinephrine, 3,4-dihydroxy-L-phenylalanine, 3,4-dihydroxyphenylacetic acid, and vanillylmandelic acid), tryptophan and its metabolites (5-hydroxyindolacetic acid, indoxyl sulfate, serotonin, and kynurenic acid) in canine mammary cancer urine samples. Our results indicated significantly increased concentrations of three tryptophan metabolites, 5-hydroxyindolacetic acid (p < 0.001), serotonin, indoxyl sulfate (p < 0.01), and kynurenic acid (p < 0.05), and 2 tyrosine metabolites, 3,4-dihydroxy-L-phenylalanine (p < 0.001), and epinephrine (p < 0.05) in urine samples from the mammary gland tumor group compared to concentrations in urine samples from the healthy group. The results indicate that select urinary tyrosine and tryptophan metabolites may be useful as non-invasive diagnostic markers as well as in developing a therapeutic strategy for canine mammary gland tumors.

• Journal of the Korean Magnetic Resonance Society
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• v.14 no.1
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• pp.28-37
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• 2010

Metabolites of urine samples from 6 colorectal cancer patients were analyzed by two-dimensional NMR spectroscopy, where the samples were collected before and after the surgical treatments per patient. NMR data were analyzed with the help of the metabolome database and the statistics software. Urine samples before and after the treatments showed significantly different metabolic profiles from each other. We were able to compare 10 different metabolites. Most of the assigned metabolites of every patient showed a tendency of increase after the surgery except for a few cases. The amount of changes in individual metabolites varied significantly from patient to patient, but the combination of such changes could be used to distinguish the condition before the surgery from after, which could be done by PCA analysis. The analysis via $^{1}H-^{13}C$ HSQC spectra proved to be applicable in assessing and classifying global metabolic profiles of the urines from colorectal cancer patients.

• Analytical Science and Technology
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• v.21 no.6
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• pp.510-517
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• 2008

This study has been described the metabolism and excretion in a healthy male urine collected for 26hrs after oral administration of diclofenac. To detect conjugated metabolites of diclofenac, urine sample was acid-hydrolyzed under the conditions of 6M-HCl at over $110^{\circ}C$ for 1hr. During the acidic hydrolysis process, diclofenac and its metabolites were converted into their corresponding lactam-ring through dehydration reaction. As results of chemical conversion by means of hydrolysis, the structures of diclofenac and its metabolites were also changed acidic to basic forms. However, lactam-ring was degraded by hydroxyl ion at basic condition. Thus, the extraction rate of dehydrated diclofenac and its metabolites was not favored at basic condition. For the determination of trace amounts of diclofenac and its metabolites in urine, trimethylsilylation (TMS) with MSTFA was applied and followed by analysis with gas chromatograph-mass spectrometer. In this study, four metabolites that are formed by the hydroxylation of parent drug were mainly detected. Each metabolite was tentatively identified by both interpretation of mass spectra and comparison with previously reported results. In addition, time profile of urinary excretion rate for parent drugs and metabolites was studied. Finally, the metabolic pathway of diclofenac was suggested on the basis of the elucidation of its metabolites and excretion profiles.

• Annals of Occupational and Environmental Medicine
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• v.35
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• pp.53.1-53.15
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• 2023

Background: Plastics are high-molecular-weight materials composed of long carbon chains. They are prevalent in daily life, present in various items such as food containers and microwavable packaging. Phthalates, an additive used to enhance their flexibility, are endocrine-disrupting chemicals. We utilized the data from the Korean National Environmental Health Survey (KoNEHS) cycle 3, representing the general South Korean population, to investigate the relationship between the use of plastics in refrigerator food storage and phthalate exposure. Methods: We assessed 3,333 adult participants (aged ≥ 19 years) including 1,526 men and 1,807 women, using data from KoNEHS cycle 3. Using the 75th percentile concentration, urine phthalate metabolites were categorized into high and low-concentration groups. χ² test was conducted to analyze variations in the distribution of each variable, considering sociodemographic factors, health-related factors, food intake, the use of plastics, and the concentration of urine phthalate metabolites as the variables. To calculate odds ratios (ORs) for the high-concentration group of urine phthalate metabolites based on the use of plastics in refrigerator food storage, logistic regression analysis was conducted. Results: In men, the use of plastics in refrigerator food storage had significantly higher adjusted ORs compared to those using the others. The adjusted ORs were calculated as follows: mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) had an OR of 1.35 (95% confidence interval [CI]: 1.05-1.72), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) had an OR of 1.48 (95% CI: 1.16-1.88), mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP) had an OR of 1.32 (95% CI: 1.04-1.66), ∑di(2-ethylhexyl) phthalate (∑DEHP) had an OR of 1.37 (95% CI: 1.08-1.74) and mono-n-butyl phthalate (MnBP) had an OR of 1.44 (95% CI: 1.13-1.84). Conclusion: The concentrations of urine phthalate metabolites (MEHHP, MEOHP, MECPP, ∑DEHP, and MnBP) were significantly higher in men who used plastics in refrigerator food storage compared to those using the others.