• 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.

• Analytical Science and Technology
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• v.25 no.1
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• pp.19-24
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• 2012

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the quantitative determination of ertapenem in human plasma and urine. After addition of internal standard (ceftazidime), plasma and urine was diluted with methanol and analyzed by LC-MS/MS. Using MS/MS with multiple reaction monitoring (MRM) mode, ertapenem were selectively detected without severeinterference from human plasma and urine. The standard calibration curve for ertapenem was linear ($r^2$= 0.9996)over the concentration range 1~100 ${\mu}g/mL$ in human plasma. The intra- and inter-day precision over the concentration range of ertapenem was lower than 8.9% (correlation of variance, CV), and accuracy was between 97.2~106.2%. On the other hand, it was showed good relationship ($r^2$= 0.9992) and the precision (intra- and inter-day) over the concentration range of ertapenem was lower than CV 7.2%, and accuracy was between 97.9~111.6% for urine. This method has been successfully applied to the pharmacokinetic study of ertapenem in human plasma and urine.

• Journal of the Korean Magnetic Resonance Society
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• v.16 no.1
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• pp.46-66
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• 2012

Metabolomic studies using human urine have shown that human metabolism is altered by a variety of environmental, cultural, and physiological factors. Comprehensive information about normal human metabolite profiles is necessary for accurate clinical diagnosis of disease and for disease prevention and treatment. In this study, metabolite correlation analyses, using $^1H$ nuclear magnetic resonance (NMR) spectroscopy coupled with multivariate statistics, were performed on human urine to compare metabolic differences based on gender and/or obesity in healthy human subjects. First, we applied partial least squares discriminant analysis to the NMR spectral data set to verify the data's ability to discriminate by gender and obesity. Then, the differences in metabolite-metabolite correlation between male and female, and between normal and high body mass index (obese) subjects were investigated through pairwise correlations. Creatine and several metabolites, including isoleucine, trans-aconitate, and trimethylamine N-oxide (TMAO), exhibited different quantitative relationships depending on gender. Dimethylamine had a different correlation with glycine and TMAO, based on gender. The correlation of TMAO with amino acids was considerably lower in obese, compared to normal, subjects. We expect that the results will shed light on the metabolic pathways of healthy humans and will assist in the accurate diagnosis of human disease.

• Bulletin of the Korean Chemical Society
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• v.27 no.10
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• pp.1604-1608
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• 2006

A simple and efficient cloud point extraction-spectrofluorimetric method for the determination of thiamine in human urine is proposed. The procedure is based on the oxidation of thiamine with ferricyanide to form thiochrome, its extraction to Triton X-114 micelles and spectrofluorimetric determination. The variables affecting oxidation of thiamine, extraction and phase separation were studied and optimized. Under the experimental conditions used, the calibration graphs were linear over the range 2.5-1000 ng $mL^{-1}$. The limit of detection was 0.78 ng $mL^{-1}$ of thiamine and the relative standard deviation for 5 replicate determinations of thiamine at 400 ng $mL^{-1}$ concentration level was 2.42%. Average recoveries between 93-107% were obtained for spiked samples. The proposed method was applied to the determination of thiamine in human urine.

• Archives of Pharmacal Research
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• v.19 no.6
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• pp.566-569
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• 1996

A sensitivity method has been developed for the detection and determination of niflmic acid(NA) in human urine. Samples were extracted with diethylether. Flunixin (FN) was added to the sample prior to extraction as an internal standard. Niflumic acid was converted to its methyl derivative and analyzed by capillary gas chromatography/negative chemical isonization mass spectrometry. Using selected ion monitoring (SIM), the levels of NA down to 5 pg/ml could be detected in 5 ml spiked urine sample. Calibration curve was linear over the range of 0.5 ppm-50 ppm. The recovery of niflumic acid from urine at 40 pg/ml was to be $91.7{\pm}3.8(n=3)$ and the coefficient of variation was 4.1%.

• Proceedings of the Korean Institute of Electrical and Electronic Material Engineers Conference
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• 2006.06a
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• pp.396-397
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• 2006

The novel urine-activated microbatteries have been successfully demonstrated. In this microbattery, a magnesium (Mg) layer and copper chloride (CuCl) in the filter paper are used as the anode and the cathode, respectively. A stack consisting of a Mg layer, CuCl-doped filter paper and a copper (Cu) layer sandwiched between two plastic layers is hot-pressed into the microbatteries at $100^{\circ}C$. The microbatteries can be activated by adding a droplet of human urine. The experimental results show that the microbattery can deliver a maximum voltage of 1.4 V and maximum power of 1.96 mW for the $1\;k{\Omega}$ load resistor.

• Bulletin of the Korean Chemical Society
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• v.19 no.1
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• pp.45-50
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• 1998

Most organophosphorus pesticides may be metabolized to yield some common phosphates in human or in animals, and these metabolites may be used as the exposure biomarkers to pesticides. In this study, we developed the extraction method of four phosphate metabolites from the spiked human urine in high recovery by the solid phase extraction with a reverse-phase cartridge (cyclohexyl silica) followed by the elution with methanol. The extracted urinary metabolites were derivatized with hexamethyldisilazane/trimethyl-chlorosilane/pyridine (2 : 1 : 10, v/v/v) and identified by gas chromatography/mass spectrometry. Calibration curve obtained from each metabolite standard using by GC/MS/SIM has shown good linearity and detection limits of metabolites were the range of 0.05-0.1 ㎍/㎖ in urine. Phenthoate, one of the organophosphorus pesticides, was orally administrated to rats. Four metabolites were detected in the rat urine. The results of this study may be applied to development of exposure biomarkers for monitoring of environmental pollutants.

• Mass Spectrometry Letters
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• v.9 no.4
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• pp.95-99
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• 2018

An innovative, simple, and rapid assay method based on liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was developed and validated for the simultaneous determination of eight statin drugs in human urine. A simple sample clean-up procedure using the "dilute and shoot" (DAS) approach enabled a fast and reliable analysis. The influence of the dilution factor was investigated to ensure detectability and reduce the matrix effect. Chromatographic separation was performed on a Phenomenex Kinetex C18 column ($50{\times}3.0mm$ i.d., $2.6{\mu}m$) using an elution gradient of mobile phase A composed of 0.1% acetic acid, and mobile phase B composed of acetonitrile, at a flow rate of 0.35 mL/min. Quantitation was performed on a triple quadrupole mass spectrometer operated in multiple reaction monitoring (MRM) mode using electrospray ionization in positive ion mode. The total chromatographic run time was 15 min. The method was validated for selectivity, sensitivity, recovery, linearity, accuracy, precision, and stability. The present method was successfully applied to the analysis of Rosuvastatin in urine samples after oral administration to healthy human subjects.

• 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 Engineering Research
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• v.12 no.3
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• pp.93-100
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• 2007

I improved an analytical method for determining trace amounts of eleven phenolic endocrine-disrupting chemicals (11 phenolic EOCs) in human urine. The 11 phenolic EOCs were subjected to hydrolysis and then to solid phase extraction with a XAD-4 column. Alkylphenols, chlorophenols, and bisphenol A in XAD-4 column were eluted with acetonitrile, and the eluate was concentrated under a nitrogen stream, and then tert-butyldimethylsilylation. Separation and determination were done by gas chromatography, using mass spectrometry operating in the selective ion monitoring mode for quantitation. For tert-butyldimethylsily (TBDMS) derivatization the recoveries were $91.2{\sim}125.9%$, the limits of quantitation (LOQ) for the 11 phenolic EOCs in the nanogram-per-milliliter range ($0.025{\sim}1.000\;ng/mL$) were thus achieved by using 1 mL of urine, and the SIM responses were linear with the correlation coefficient varying by $0.9300{\sim}0.9943$. Based on the results for urine samples from unexposed individuals, 4-tert-octylphenol and pentachlorophenol were detected in hydrolysed urine sample. Other alkylphenols, chlorophenols and bisphenol A were not detected.