• Mass Spectrometry Letters
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• v.4 no.3
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• pp.47-50
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• 2013

An ultra-fast generic LC-MS/MS method was developed for high-throughput quantification of discovery pharmacokinetic (PK) samples and its reliability was verified. The method involves a simple protein precipitation for sample preparation and the analysis by ultra-fast generic LC-MS/MS with the ballistic gradient program and selected reaction monitoring (SRM) mode. Approximately 290 new chemical entities (NCEs) (over 10,000 samples) from 5 therapeutic programs were analyzed. The calibration curves showed good linearity in the concentration range of 1, 2 or 5 to 2000 ng/mL. No significant ion suppression was observed in the elution region of all the NCEs. When approximately 300 plasma samples were continuously analyzed, the peak area of internal standard was constant and reproducible. In the repeated analysis of samples, the plasma concentrations and the area under the curve (AUC) were consistent with the results from the first analysis. These results showed that the present ultra-fast generic LC-MS/MS method is reliable in terms of selectivity, sensitivity, and reproducibility and could be useful for high-throughput quantification and other bioanalysis in drug discovery.

• Mass Spectrometry Letters
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• v.9 no.1
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• pp.24-29
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• 2018

DC23, a triazolothione resorcinol analogue, is known to inhibit heat shock protein 90 and pyruvate dehydrogenase kinase which are up-regulated in cancer and diabetes, respectively. This study was performed to elucidate the metabolism of DC23 in human liver microsomes (HLMs). HLMs incubated with DC23 in the presence of uridine 5'-diphosphoglucuronic acid (UDPGA) and/or ${\beta}$-nicotinamide adenine dinucleotide phosphate (NADPH) resulted in the formation of four metabolites, M1-M4. M1 was identified as DC23-N-Oxide, on the basis of LC-MS/MS analysis. DC23 was further metabolized to its glucuronide conjugates (M2, M3, and M4). In vitro metabolic stability studies conducted with DC23 in HLMs revealed significant glucuronide conjugation with a $t_{1/2}$ value of 1.3 min. The inhibitory potency of DC23 on five human cytochrome P450s was also investigated in HLMs. In these experiments, DC23 inhibited CYP2C9-mediated tolbutamide hydroxylase activity with an $IC_{50}$ value of $8.7{\mu}M$, which could have implications for drug interactions.

• Mass Spectrometry Letters
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• v.9 no.1
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• pp.30-36
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• 2018

A quantitation method for free amino acids in human serum was developed using a stepwise-dilution method and a bimodal cation exchange (CEX)/hydrophilic interaction liquid chromatography (HILIC)-tandem mass spectrometry system equipped with an electrospray ionization source (ESI/MS/MS). This method, which was validated using quality control samples, was optimized for enhanced selectivity and sensitivity. Dithiothreitol (DTT) was used as a reducing agent to prevent the oxidation of a serum sample ($50{\mu}L$), which was then subjected to stepwise dilution using 3, 30, and 90 volumes of acetonitrile containing 0.1% formic acid. Chromatographic separation was performed on an Imtakt Intrada Amino Acid column ($50mm{\times}3mm$, $3{\mu}m$) in mixed mode packed with CEX and HILIC ligands embedded in the stationary phase. Underivatized free amino acids were eluted and separated within 10 min. As a result of the validation, the precision and accuracy for the inter- and intraday assays were determined as 2.11-11.51% and 92.82-109.40%, respectively. The lowest limit of quantification (LLOQ) was $0.5-4.0{\mu}g/mL$ and the matrix effect was 80.22-115.93%. The proposed method was successfully applied to the quantitative analysis of free amino acids in human serum.

• Mass Spectrometry Letters
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• v.8 no.2
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• pp.23-28
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• 2017

Arctigenin is the main active ingredient of Fructus Arctii, which has been reported with a variety of therapeutic activities including anti-cancer, anti-inflammation, anti-virus, and anti-obesity effects. In this study, a simple and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the determination of arctigenin in rat plasma. The assay utilized a simple protein precipitation with methanol and the mobile phase consisted of 100% methanol and water containing 0.1% formic acid (65:35 v/v). Arctigenin and the internal standard (psoralen) were monitored using a positive electrospray turbo ionspray mode with multiple reaction monitoring transitions of m/z $373.2{\rightarrow}136.9$ and m/z $187.2{\rightarrow}130.9$, respectively, and total chromatographic run time was within 5 min. The lower limit of quantification (LLOQ) of arctigenin was 5 ng/mL in the rat plasma. The intra- and inter-day accuracy of arctigenin at LLOQ and matrix-matched quality control samples ranged 97.4 - 104.8% and 97.2 - 102.0%, respectively. The intra-day precision was within 4.80% and the inter-day precision was within 5.92%. Application of the present method was demonstrated through a pharmacokinetic study after intravenous and oral administration of arctigenin in male Sprague Dawley rats.

• Proceedings of the Korea Water Resources Association Conference
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• 2016.05a
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• pp.17-17
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• 2016

이중편파 레이더는 수평 수직반사도($Z_H{\cdot}Z_V$), 차등반사도($Z_{DR}$), 교차상관계수(${\rho}_{HV}$), 차등위상차(${\Phi}_{DP}$) 등 다양한 변수 산출을 통하여 대기 수상체 구분, 우적분포에 영향이 적은 강우량 추정, 밝은 띠(BB, Bright Band)의 탐지 등이 가능하게 됨으로써 수문기상 및 재해관리 분야에 활용성이 점점 더 커지고 있다. 본 연구는 RHI, PPI에서 생산된 레이더 변수를 이용하여 BB를 탐지하고 그 특성을 평가하였다. BB는 레이더를 이용하여 상층대기를 관측할 때 수직단면에서 강수입자가 눈에서 비로 변하는 구간에서 과대하게 높은 반사도가 나타나는 층을 말한다. BB에서는 QPE가 과대 추정되기 때문에, BB의 특성 파악은 레이더의 관측전략 수립과 QPE 보정에 필수적이다. 본 연구에서는 RHI에 의한 $Z_H$의 연직단면분석, RHI와 PPI의 고도각 경사거리(slant range) 빔의 ${\rho}_{HV}$, $Z_{DR}$, $Z_H$에 의한 분석을 통하여 BB의 상단부($BB_{TOP}$), 최정점($BB_{PEAK}$) 및 하단부($BB_{BOTTOM}$)의 고도를 상호 비교 평가하였다. 분석 자료는 KICT X-밴드 레이더에 의한 관측한 2015년 10월 21일의 층상운에 의한 강우를 이용하였다. RHI에 의한 $Z_H$의 연직단면 분석결과 $BB_{top}$, $BB_{bottom}$ 및 $BB_{peak}$는 KICT 레이더 고도(MSL : 40m)를 기준으로 각각 3.26Km, 2.3Km($BB_{width}$: 0.96km) 및 2.7Km로 나타났다. 이 같은 결과는 다른 2가지 분석방법에서도 유사하게 나타나고 있으며, 이는 BB분석을 위해 다양한 변수를 통한 신뢰성 있는 BB의 특성을 파악할 수 있는 기반을 제공한다.

• Mass Spectrometry Letters
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• v.12 no.4
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• pp.179-185
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• 2021

Collision-induced dissociation (CID) combined with electrospray ionization mass spectrometry (ESI-MS) was used to obtain structural information on rat islet amyloid polypeptide (rIAPP) monomers (M) and dimers (D) observed in the multiply charged state in the MS spectrum. MS/MS analysis indicated that the rIAPP monomers adopt distinct structures depending on the molecular ion charge state. Peptide bond dissociation between L₂₇ and P₂₈ was observed in the MS/MS spectra of rIAPP monomers, regardless of the monomer molecular ion charge state. MS/MS analysis of the dimers indicated that D⁵⁺ comprised M²⁺ and M³⁺ subunits, and that the peptide bond dissociation process between the L₂₇ and P₂₈ residues of the monomer subunit was also maintained. The observation of (M+ b₂₇)⁴⁺ and (M+ y₁₀)³⁺ fragment ions were deduced to originate from the two different D⁵⁺ complex geometries, the N-terminal and C-terminal interaction geometries, respectively. The fragmentation pattern of the [M_rIAPP + M_hIAPP]⁵⁺ MS/MS spectrum showed that the interaction occurred between the two N-terminal regions of M_rIAPP and M_hIAPP in the heterogeneous dimer (hetero-dimer) D⁵⁺ structure.

• Mass Spectrometry Letters
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• v.12 no.4
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• pp.200-205
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• 2021

Polynemoraline C, a pyridocoumarin alkaloid, exhibits anticholinergic, anti-inflammatory, antitumor, and antimicrobial activities. A sensitive analytical method of polynemoraline C in mouse plasma was developed and validated using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Polynemoraline C and ¹³C-caffeine (internal standard) in mouse plasma were extracted using a liquid-liquid extraction method coupled with ethyl acetate. This extraction method resulted in high and reproducible extraction recovery in the range of 73.49%-77.31% with no interfering peaks around the peak retention time of polynemoraline C and ¹³C-caffeine. The standard calibration curves for polynemoraline C were linear over the range of 0.5-200 ng/mL with r² > 0.985. The accuracy, precision, and the stability of the data were within acceptable limits on the FDA guideline. After intravenous and oral administration of polynemoraline C at doses of 5 and 30 mg/kg, respectively, the present method was successfully applied to the pharmacokinetic study of polynemoraline C. Polynemoraline C in mouse plasma showed a multi-exponential elimination pattern with a high volume of distribution values. This compound's absolute oral bioavailability was found to be 17.0%. Polynemoraline C's newly developed LC-MS/MS method can be used for further studies on the efficacy, toxicity, and biopharmaceutics of polynemoraline C, as well as its pharmacokinetic studies.

• Mass Spectrometry Letters
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• v.12 no.4
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• pp.192-199
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• 2021

Alpine glaciers harbor a large quantity of bio-labile dissolved organic matter (DOM), which plays a pivotal role in global carbon cycling as glacial-fed streams are headwaters of numerous large rivers. To understand the complexity, origin, and fate of DOM in glaciers and downstream-linked streams and lakes, we elucidated the molecular composition of DOM in two different Tibetan Plateau glaciers, eight glacial-fed streams and five lakes, using an ultrahigh-resolution 15 Tesla Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer. The compositional changes of the DOM samples revealed that glacier DOM mostly exhibited sulfur-containing organic compounds (CHOS species). We also found that aliphatic formulae contributed more than 50% of the total abundance of assigned molecules in glacier samples, and those compounds were significantly related to CHOS species. The CHO proportions of glacial-fed streams and lakes samples increased with increasing distance from glacial terminals. The relative contribution of terrestrial-derived organics (i.e., lignins and tannins) declined while microbial-originated organics (aliphatics) increased with increasing elevation. This suggested the gradual input of allochthonous materials from non-glacial environment and the degradation of microbe-derived compounds along lower elevations. Alpine glaciers are retreating as a result of climate change and they nourished numerous streams, rivers, and downstream-linked lakes. Therefore, the interpretations of the detailed molecular changes in glacier ice, glacial-fed streams, and alpine lakes on the Tibetan Plateau could provide broad insights for understanding the biogeochemical cycling of glacial DOM and assessing how the nature of DOM impacts fluvial ecosystems.

• Mass Spectrometry Letters
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• v.10 no.2
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• pp.61-65
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• 2019

Korean ginseng (Panax ginseng Meyer) is a traditional herb used across the world to treat various diseases. Although, red ginseng is this herb's most famous product and has demonstrated diverse pharmacological activities, white ginseng (WG) is another ginseng product that is made fresh and individually regulated in Eastern Asia. Red and white ginseng show different characteristics due to distinct processing steps despite originating from the same plant, and the drug interactions induced by WG have not been well documented. Selegiline is a selective monoamine oxidase (MAO) inhibitor used as an antidyskinetic and antiparkinsonian agent. Here we developed a quantification method for selegiline in mouse plasma using a C8 stationary phase in triple quadrupole-mass spectrometry (LC-MS/MS) with multiple reaction monitoring (MRM). The validated LC-MS/MS method was successfully applied to determine the potential interaction with WG extract (0.1 g/kg/day) pre-administered for 4 weeks. The $AUC_{0-240min}$ of selegiline was altered due to a decrease in the absorption of selegiline with repeated administration of WG extract.

• Mass Spectrometry Letters
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• v.10 no.2
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• pp.43-49
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• 2019

The aim of this study was conducted to develop an analytical method to determine the concentration of ceftiofur residue in eel, flatfish, and shrimp. For derivatization and extraction, the sample was hydrolyzed with dithioerythritol to produce desfuroylceftiofur, which was then derivatized by iodoacetamide to obtain desfuroylceftiofur acetamide. For purification, the process of solid phase extraction (Oasis HLB) was used. The target analytes were confirmed and quantified in $C_{18}$ column using liquid chromatography-tandem mass spectrometry with 0.1% formic acid in water (A) and 0.1% formic acid in acetonitrile (B) as the mobile phase. The linearity of the standard calibration curve was confirmed by a correlation coefficient, $r^2>0.99$. The limit of quantification for ceftiofur was 0.002 mg/kg; the accuracy (expressed as the average recoveries) was 80.6-105%; the precision (expressed as the coefficient of variation) was below 6.3% at 0.015, 0.03, and 0.06 mg/kg. The validated method demonstrated high accuracy and acceptable sensitivity to meet the Codex guideline requirements. The developed method was tested using market samples. As a results, ceftiofur was detected in one sample. Therefore, it can be applied to the analysis of ceftiofur residues in fishery products.