• The Korean Journal of Physiology and Pharmacology
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• v.21 no.1
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• pp.45-54
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• 2017

Our study aims to determine the metabolism and excretion of novel pulmonary-targeting docetaxel liposome (DTX-LP) using the in vitro and in vivo animal experimental models. The metabolism and excretion of DTX-LP and intravenous DTX (DTX-IN) in New Zealand rabbits were determined with ultra-performance liquid chromatography tandem mass spectrometry. We found DTX-LP and DTX-IN were similarly degraded in vitro by liver homogenates and microsomes, but not metabolized by lung homogenates. Ultra-performance liquid chromatography tandem mass spectrometry identified two shared DTX metabolites. The unconfirmed metabolite $M_{un}$ differed structurally from all DTX metabolites identified to date. DTX-LP likewise had a similar in vivo metabolism to DTX-IN. Conversely, DTX-LP showed significantly diminished excretion in rabbit feces or urine, approximately halving the cumulative excretion rates compared to DTX-IN. Liposomal delivery of DTX did not alter the in vitro or in vivo drug metabolism. Delayed excretion of pulmonary-targeting DTX-LP may greatly enhance the therapeutic efficacy and reduce the systemic toxicity in the chemotherapy of non-small cell lung cancer. The identification of $M_{un}$ may further suggest an alternative species-specific metabolic pathway.

• Analytical Science and Technology
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• v.30 no.4
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• pp.194-204
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• 2017

Direct injection (DI) and solid phase extraction (SPE) methods for the simultaneous determination of pendimethalin (PDM) and dinoseb (DNS) in environmental water have been optimized using the ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method. The limits of quantification (LOQs) of PDM and DNS were $0.01{\mu}g/L$ using the DI method and $0.0001-0.0002{\mu}g/L$ using the SPE method. The precision by SPE UPLC-MS/MS was less than 11 % for intra-day and inter-day analyses. When the proposed SPE method was used to analyze two analytes in environmental water, PDM was detected in a concentration range of $0.0002-0.011{\mu}g/L$ in 31 samples of the 114 surface water samples, and DNS was detected in a concentration range of $0.0005-0.045{\mu}g/L$ in 17 samples of the 114 surface water samples analyzed. When the DI method was used to analyze target compounds in the same samples, the detected concentrations of the two analytes were within 21% in samples with concentrations above $0.01{\mu}g/L$. The DI UPLC-MS/MS method can thus be used for the routine monitoring of PDM and DNS in environmental water, and the SPE LC-MS/MS method can be used for the determination of the ultra-trace PDM and DNS residues in environmental water.

• Food Science of Animal Resources
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• v.43 no.5
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• pp.914-937
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• 2023

The objective of this study was to establish a multi-residue quantitative method for the analysis of anthelmintic and antiprotozoal drugs in various livestock products (beef, pork, and chicken) using ultra-high-performance liquid chromatography-tandem mass spectrometry. Each compound performed validation at three different levels i.e., 0.5, 1, and 2× the maximum residue limit according to the CODEX guidelines (CAC/GL 71-2009). This study was conducted according to the modified quick, easy, cheap, effective, rugged, and safe procedure. The matrix-matched calibrations gave correlation coefficients >0.98, and the obtained recoveries were in the range of 60.2%-119.9%, with coefficients of variation ≤32.0%. Furthermore, the detection and quantification limits of the method were in the ranges of 0.03-3.2 and 0.1-9.7 ㎍/kg, respectively. Moreover, a survey of residual anthelmintic and antiprotozoal drugs was also carried out in 30 samples of beef, pork, and chicken collected in Korea. Toltrazuril sulfone was detected in all three samples. Thus, our results indicated that the developed method is suitable for determining the anthelmintic and antiprotozoal drug contents in livestock products.

• 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.36 no.2
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• pp.89-98
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• 2023

Analytical methods for detecting atranol, chloroatranol, evernic acid, (+)-usnic acid, and atranorin in sanitary napkins and mouthwashes were developed using ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). UHPLC-MS/MS conditions were optimized for rapid, sensitive, and simultaneous analysis of the five allergenic compounds. The methods were validated by assessing their specificity, matrix effects, limit of detection (LOD), limit of quantification (LOQ), linearity, accuracy, and precision. Good linearity was achieved with a determination coefficient of ≥0.99. The LOD and LOQ were 2.1-9.8 and 6.4-29.6 ng/g for sanitary napkins and 0.29-0.48 and 0.87-1.45 ng/mL for mouthwashes, respectively. The accuracy and precision were within an acceptable range according to the criteria reported in the European SANTE/11813/2017 guidelines (70-120 % recovery, <20 % relative standard deviation). Therefore, these methods can be used to analyze atranol, chloroatranol, evernic acid, (+)-usnic acid, and atranorin in sanitary napkins and mouthwashes.

• Natural Product Sciences
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• v.20 no.3
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• pp.182-190
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• 2014

An ultra-performance liquid chromatography (UPLC) coupled with electrospray ionization (ESI) tandem mass spectrometry (MS) method was established for quantitative analysis of twelve components, allantoin (1), morroniside (2), 5-hydroxymethyl-2-furfural (5-HMF) (3), loganin (4), coumarin (5), cinnamic acid (6), mesaconitine (7), cinnamaldehyde (8), hypaconitine (9), aconitine (10), alisol B (11), and alisol B acetate (12) in a Palmijihwang-hwan decoction. The twelve constituents were separated on a UPLC BEH C18 column ($2.1{\times}100mm$, $1.7{\mu}m$) at a column temperature of $40^{\circ}C$ by gradient elution with 0.1% (v/v) formic acid in water and acetonitrile as the mobile phase. The flow rate was 0.3 mL/min and the injection volume was $2.0{\mu}L$. Calibration curves of all compounds were acquired with values of the correlation coefficient ${\geq}0.99$ within the test ranges. The limits of detection and quantification for all analytes were 0.01 - 4.53 ng/mL and 0.03 - 13.60 ng/mL, respectively. The concentrations of the compounds 1 - 9 and 12 were 72.83, 4389.00, 4859.00, 3155.17, 223.67, 33.50, 1.97, 518.00, 2.25, and $25.00{\mu}g/g$, respectively. However, compounds 10 and 11 were not detected.

• Journal of Ginseng Research
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• v.44 no.6
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• pp.775-783
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• 2020

Background: The reports about valuable oligosaccharides in ginseng are quite limited. There is an urgent need to develop a practical procedure to detect and analyze ginseng oligosaccharides. Methods: The oligosaccharide extracts from ginseng were permethylated by solid-phase methylation method and then were analyzed by ultra-high-performance liquid chromatography-Q-Orbitrap/MS. The sequence, linkage, and configuration information of oligosaccharides were determined by using accurate m/z value and tandem mass information. Several standard references were used to further confirm the identification. The oligosaccharide composition in white ginseng and red ginseng was compared using a multivariate statistical analysis method. Results: The nonreducing oligosaccharide erlose among 12 oligosaccharides identified was reported for the first time in ginseng. In the comparison of the oligosaccharide extracts from white ginseng and red ginseng, a clear separation was observed in the partial least squares-discriminate analysis score plot, indicating the sugar differences in these two kinds of ginseng samples. The glycans with variable importance in the projection value large than 1.0 were considered to contribute most to the classification. The contents of oligosaccharides in red ginseng were lower than those in white ginseng, and the contents of maltose, maltotriose, maltotetraose, maltopentaose, maltohexaose, maltoheptaose, maltooctaose, maltononaose, sucrose, and erlose decreased significantly (p < 0.05) in red ginseng. Conclusion: A solid-phase methylation method combined with liquid chromatography-tandem mass spectrometry was successfully applied to analyze the oligosaccharides in ginseng extracts, which provides the possibility for holistic evaluation of ginseng oligosaccharides. The comparison of oligosaccharide composition of white ginseng and red ginseng could help understand the differences in pharmacological activities between these two kinds of ginseng samples from the perspective of glycans.

• YAKHAK HOEJI
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• v.58 no.3
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• pp.158-164
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• 2014

Dangguisu-san is a well-known traditional Korean herbal medicine prescription and has been widely used to treat ecchymosis, blood stagnation, and pain resulting from physical shock in Korea. In this study, an ultra-performance liquid chromatography-electrospray ionization-mass spectrometer method was established for the simultaneous determination of the 17 biomarker components in Dangguisu-san. All analytes were separated on an UPLC BEH $C_{18}$ ($100{\times}2.1$ mm, $1.7{\mu}m$) column and maintained at $45^{\circ}C$. The mobile phase consisted of two solvent systems, 0.1% (v/v) formic acid in water (A) and acetonitrile (B) by gradient flow. The injection volume was $2.0{\mu}l$ and the flow rate was 0.3 ml/min with detection at mass spectrometer. Calibration curves of the 17 biomarker components were acquired with $r^2$ values ${\geq}0.9951$. The values of limit of detection and quantification of all analytes were 0.02~6.32 ng/ml and 0.05~18.95 ng/ml, respectively. The amounts of the 17 components in Dangguisu-san sample were $3.17{\sim}13,224.50{\mu}g/g$.

• Journal of Microbiology and Biotechnology
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• v.28 no.7
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• pp.1094-1104
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• 2018

The peel of astringent persimmon (Diospyros kaki Thunb. cv. Cheongdo-Bansi) is a by-product of dried persimmon (gotgam). We investigated if deastringent peel extracts of persimmon cv. Cheongdo-Bansi had antioxidative and neuroprotective properties. Two different extracts were prepared: thermally and nonthermally treated persimmon peel extracts (TPE and NTPE, respectively). Both TPE and NTPE were fractionated sequentially in n-hexane, chloroform, ethyl acetate, n-butanol, and water. The TPE and NTPE ethyl acetate fractions had the highest total phenolic and flavonoid contents as well as antioxidant capacities among all the fractions. Pretreatment of neuronal PC-12 and SH-SY5Y cells with the TPE and NTPE ethyl acetate fractions increased cell viability after exposure to oxidative stress. The ethyl acetate fraction of TPE attenuated oxidative stress inside both PC-12 and SH-SY5Y cells more effectively than that of NTPE. Furthermore, the TPE and NTPE ethyl acetate fractions inhibited acetylcholinesterase and butyrylcholinesterase. Analysis of ultra-high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry results revealed gallic acid, kaempferol, kaempferol-3-O-galactoside, kaempferol-3-O-glucoside, quercetin, quercetin3-O-galactoside, quercetin-3-O-galactoside-2'-O-gallate, and quercetin-3-O-glucoside as the major phenolics of the TPE and NTPE ethyl acetate fractions. Taken together, these results suggest that the ethyl acetate fraction of deastringent persimmon peel is rich in antioxidants and has potential as a functional food to reduce oxidative stress.

• Korean Journal of Veterinary Research
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• v.56 no.4
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• pp.233-239
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• 2016

This study was conducted to analyze penicillin G (PEG), streptomycin (STR) and neomycin (NEO) residues in milk of healthy lactating cows. Milk samples were collected from all four quarters of 12 dairy cows 2−7 days after intramammary infusions of an ointment containing PEG, STR and NEO once (n = 4; group I) or twice (n = 4, group II) daily. Ultra-performance liquid chromatography coupled with electrospray tandem mass spectrometry was used to determine the antibiotic residues in the samples. The correlation coefficient ($r^2$) of the calibration curves for all antibiotics was > 0.999 and the limits of detection and quantification were $0.002-0.005{\mu}g/mL$ and $0.007-0.02{\mu}g/mL$, respectively. Recovery rates were ranged from 75.5 to 92.3%. In group I, PEG, STR and NEO residues were detected in milk at 2, 3 and 2 days post-treatment, respectively, which were below the maximum residue limit (MRL). In group II, PEG, STR and NEO residues were detected in milk at 2, 3 and 3 days post-treatment, respectively, which were bellow the MRL. These results suggest that a 3-day for milk withdrawal period after the ointment treatment might be sufficient for reduction of the antibiotic residues below the MRL.