• Mass Spectrometry Letters
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• 제7권3호
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• pp.69-73
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• 2016

High-resolution quadrupole-Orbitrap mass spectrometry (HRMS), with high-resolution (> 10,000 at full-width at half-maximum) and accurate mass (< 5 ppm deviation) capabilities, plays an important role in the structural elucidation of drug metabolites in the pharmaceutical industry. ML106, a derivative of imidazobenzimidazole, decreased melanin content and tyrosinase activity in a dose-dependent manner. Here, we investigated the phase 1 metabolic pathway of ML106 using HRMS in human liver microsomes (HLMs) and recombinant cDNA-expressed cytochrome P450 (CYP). After the incubation of ML106 with pooled HLMs and recombinant cDNA-expressed CYP in the presence of NADPH, five phase 1 metabolites, including three mono-hydroxylated metabolites (M1-3) and two di-hydroxylated metabolites (M4 and M5), were investigated. The metabolite structures were postulated by the elucidation of protonated mass spectra using HRMS. The CYP isoforms related to the hydroxylation of ML106 were studied after incubation with recombinant cDNA-expressed CYP. Here, we identified the phase 1 metabolic pathway of ML106 induced by CYP in HLMs.

• Mass Spectrometry Letters
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• 제7권3호
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• pp.55-63
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• 2016

Growth hormone (GH)-releasing peptides (GHRPs) and GH secretagogues (GHSs) are listed in the World Anti-Doping Agency (WADA) Prohibited List. In the present study, we developed and validated a method for the simultaneous analysis of seven GHRPs (alexamorelin, GHRP-1, -2, -4, -5, -6, and hexarelin) and three GHSs (anamorelin, ibutamoren, and ipamorelin) in human urine. Method validation was performed at minimum required performance levels specified by WADA technical documents (2 ng/mL) for all substances, and the method was validated with regard to selectivity (no interference), linearity (R2 > 0.9986), matrix effects (50.0%-141.2%), recovery (10.4%-100.8%), and intra- (2.8%-16.5%) and inter-day (7.0%-22.6%) precisions. The limits of detection for screening and confirmation were 0.05-0.5 ng/mL and 0.05-1 ng/mL, respectively.

• Mass Spectrometry Letters
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• 제8권3호
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• pp.59-64
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• 2017

In clinical diagnosis, it's well known that the abnormal level of uric acid (UA) in human body is implicated in diverse human diseases, for instance, chronic heart failure, gouty arthritis, diabetes, and so on. As a primary method, an isotope dilution mass spectrometry (IDMS) has been used to obtain the accurate quantity of UA in blood or serum and also develop the certificated reference material (CRM) so as to provide a SI-traceability to clinical laboratories. Due to the low solubility of UA in water, an ammonium hydroxide ($NH_4OH$) has been considered as a promising solvent to increase the solubility of UA that enables the preparation of both UA and its isotope standard solution for next IDMS-based absolute quantification. But, because of using this $NH_4OH$ solvent, it gives rise to the unwanted degradation of UA. In this study, we sought to optimize condition for the stability of UA in $NH_4OH$ solution by varying the mole ratios of UA to $NH_4OH$, followed by ID-LC-MRM analysis. In addition, we also inspected minutely the effect of the storage temperatures. Additionally, we also performed the quantitative analysis of UA in the KRISS serum certificated reference material (CRM, 111-01-02A) with diverse mixing ratios of UA to $NH_4OH$ and then compared those values to its certification value. Based on our experiments, adjusting the mole ratio of 1/2 ($UA/NH_4OH$) with the storage temperature of $-20^{\circ}C$ is an effective way to secure both the solubility and stability of UA in $NH_4OH$ solution for next IDMS-based quantification of UA in serum.

• Mass Spectrometry Letters
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• 제2권1호
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• pp.1-7
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• 2011

China's rapid economic growth has resulted in significant environmental side effects. Therefore, China has been interested in reducing her dependence on foreign oil and gas by developing technologies needed for hydrogen, in addition to her increasing energy mix of nuclear and renewable energy form, such as solar and wind power. There are three isotopes of hydrogen, i.e. protium (P or H), deuterium (D), and tritium (T). Both deuterium and tritium are important materials in nuclear fuel cycle industry. Tritium is one of the critical radioactive nuclides. Planning for and implementing contamination control as a part of normal operation and maintenance activities is an important function in any hydrogen facility, especially tritium facility. The development of hydrogen isotopes analysis is the key issues in this area. Mass spectrometry (MS) with medium (about 600) and high resolution (> 1,400) is commercially available; however, the routine analysis of hydrogen isotopes is done with low-resolution MS (< 200) in China. This paper summarizes the progress of MS measurement technology for hydrogen isotope abundance in China, focusing on our lab's research program and technical status. An analyzing method has been introduced for accurate measurement of tritium abundance in the H.D.T system by low resolution MAT-253 MS. The quotient of compression ratio coefficient is determined by building up equipment for laboratory-scale preparation of secondary standard gases and by considering the difference in sensitivity between hydrogen isotopes. The results show that the measured value is reproducible within the relative error range of 0.8% for gas samples of different tritium abundance.

• Mass Spectrometry Letters
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• 제11권2호
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• pp.36-40
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• 2020

Untargeted metabolomics is a useful tool for drug development focusing on novel chemotherapeutic and chemopreventative agents against cancer cells. In recent years, quadrupole time of flight liquid chromatography-mass spectrometry (Q-TOF LC/MS)-based untargeted metabolomic approaches have gained importance to evaluate the effect of these agents at the molecular level. The researchers working on cell culture studies still do not apply standardized methodologies on sample preparation for untargeted metabolomics approaches. In this study, the rough and wet lysis techniques performed on MCF-7 breast cancer cells were compared with each other via the Q-TOF LC/MS-based metabolomic approach. The C18 and hydrophilic interaction liquid chromatography (HILIC) columns were used for the separation of the metabolites in MCF-7 cell lysates. 505 peaks were detected through the HILIC column and 551 peaks were found through the C18 column for the wet lysis technique. This situation supported by the base peak chromatograms showed that the wet lysis technique allowed us to extract higher number of non-polar metabolites. Almost equal number of metabolites was found for the C18 and HILIC columns (697 peaks for the HILIC column and 695 peaks for the C18 column) when the rough lysis technique was used. However, the intensities of polar metabolites were higher for the rough lysis technique on base peak chromatograms for both the HILIC and C18 columns. Although cell lysis technique, which is the first step in the sample preparation for cell culture studies, does not cause dramatic differences in the number of the detected metabolite peaks, it affects the polar and non-polar metabolite ratio significantly. Therefore, it must be considered carefully especially for in vitro drug development studies.

• 한국수산과학회지
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• 제34권6호
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• pp.594-599
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• 2001

돌산도 모래해안 쇄파대에서 셀매네트를 사용하여 1 m 수심의 표층, 저층 그리고 바닷가에서 주야, 조석 계절에 따른 요각류 Acartia omorii이 출현량을 조사하였다. A. omorii의 출현량은 표층과 바닷가에 비해 저층에서 많았으며, 계절별로는 겨울철에 가장 많았다. 또 연구기간 동안 A. omorii의 출현량은 항상 밀물일 때보다 썰물일 때 많이 나타났다. A. omorii의 분포양상은 주야보다 조석 영향이 더 큰 것으로 나타났고, 대조 때는 강한 조류가 주야수직양상에 영향을 나타냈다. 겨울철에는 주야보다 조석주기 영향이 더 큰 것으로 나타났다. 겨울철에 A. omorii는 소조 때 주야수직이동을 하였고, 반면에 대조 때에는 역 주야수직이동을 했다. 소조 때 분포중심은 평균해수면 아래 $50\~100cm$층에 위치했으며, 대조 때는 약간 위쪽으로 분포중심 이 이동했다.

• 한국항해항만학회지
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• 제29권4호
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• pp.327-333
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• 2005

Sea level (MSL, MHWL, or MLWL) change has been main concern to scientists and engineers and it can be primarily due to both change of climate and vertical movement of land. This paper reports the intensive analysis of the sea level changes and broad discussion of the future at the southwestern coast of Korean peninsula. Regression analysis was conducted to investigate general tendency and periodicity of the sea levels at the six different study sites such as Gunsan-I(inner port), Gunsan-O(outer port), Mokpo, Yeosu, Heuksan and Jeju and the results were compared with global values. Besides the changes of sea levels due to global warming, the influence of the man-made structure such as seadike and seawall was attempted to quantify using the minimization of the Root Mean Square(RMS) error. The results show that it is a general tendency that the values of mean sea level rise at the southwestern coast of Korean Peninsula, especially at Gunsan-I and Jeju, are somewhat larger compared to global average values. There is also some evidence that tidal amplifications are found just after construction of man-made structure at Gunsan-I and Mokpo. However, both sites show different mechanism in relation to tidal choking, tidal flat and river discharge. The impact due to construction of man-made structure is considerably larger at Mokpo site, while the impacts due to man-made structure and the effect of sea level rise are relatively identical at Gunsan-I site. This study is expected to provide some intuition to future design.

• 한국항해항만학회:학술대회논문집
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• 한국항해항만학회 2009년도 공동학술대회
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• pp.19-20
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• 2009

국제해사기구(International Maritime Organization, IMO)에서는 선박의 해상 충돌을 방지하기 위하여 SOLAS Chapter 5의 요구조건에 따라 모든 선박에 대하여 선박자동식별장치(Automatic Identification System, AIS)를 의무적으로 장착하도록 권고하고 있다. AIS를 사용하면 타선에 대한 제원 및 항행정보의 획득이 가능하여 충돌방지뿐만 아니라 광역관제, 조난 선박의 탐색구조 등 안전관리에도 활용이 가능하다. 본 논문에서는 AIS 장비를 사용하여 ADS-B(Automatic Dependent Surveillance-Broadcast) 개념 기반의 항공감시용 송수신기를 구현한 결과에 대하여 살펴보도록 한다. 기본적으로 AIS는 해상에서 사용되기 때문에 고도 정보를 사용하지 않지만, AIS 장비 내부에 사용하는 GIS 칩셋에서 제공하는 고도 정보의 추출이 가능하다. 고도 정보를 포함한 감시 메시지 형식을 정의하고, SOTDMA(Self-Organizing Time Division Multiple Access) 방식을 개선하여 ADS-B 송수신기를 구현하였다. 적용 결과를 확인하기 위하여 지상시험 및 비행시험을 수행하였다.

• Mass Spectrometry Letters
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• 제5권3호
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• pp.84-88
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• 2014

Licoricidin isolated from Glycyrrhiza uralensis is known to have anticancer, anti-nephritic, anti-Helicobacter pylori, and antibacterial effects. In this study, a cocktail probe assay and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were used to investigate the modulating effect of licoricidin on cytochrome P450 (CYP) enzymes in human liver microsomes. When licoricidin was incubated at $0-25{\mu}m$ with CYP probes for 60 min at $37^{\circ}C$, it showed potent inhibitory effects on CYP2B6-catalyzed bupropion hydroxylation and CYP2C9-catalyzed diclofenac 4'-hydroxylation with half maximal inhibitory concentration ($IC_{50}$) values of 3.4 and $4.0{\mu}m$, respectively. The inhibition mode of licoricidin was revealed as competitive, dose-dependent, and non-time-dependent, and following the pattern of Lineweaver-Burk plots. The inhibitory effect of licoricidin has been confirmed in human recombinant cDNA-expressed CYP2B6 and 2C9 with $IC_{50}$ values of 4.5 and $0.73{\mu}m$, respectively. In conclusion, this study has shown the potent inhibitory effect of licoricidin on CYP2B6 and CYP2C9 activity could be important for predicting potential herb-drug interactions with substrates that mainly undergo CYP2B- and CYP2C9-mediated metabolism.

• Mass Spectrometry Letters
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• 제5권3호
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• pp.63-69
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• 2014

In this study, we present a new isotope-coded carbamidomethylation (iCCM)-based quantitative proteomics, as a complementary strategy for conventional isotope labeling strategies, with providing the simplicity, ease of use, and robustness. In iCCM-based quantification, two proteome samples can be separately isotope-labeled by means of covalently reaction of all cysteinyl residues in proteins with iodoacetamide (IAA) and its isotope (IAA-$^{13}C_2$, $D_2$), denoted as CM and iCCM, respectively, leading to a mass shift of all cysteinyl residues to be + 4 Da. To evaluate iCCM-based isotope labeling in proteomic quantification, 6 protein standards (i.e., bovine serum albumin, serotransferrin, lysozyme, beta-lactoglobulin, beta-galactosidase, and alpha-lactalbumin) isotopically labeled with IAA and its isotope, mixed equally, and followed by proteolytic digestion. The resulting CM-/iCCM-labeled peptide mixtures were analyzed using a nLC-ESI-FT orbitrap-MS/MS. From our experimental results, we found that the efficiency of iCCM-based quantification is more superior to that of mTRAQ, as a conventional nonisobaric labeling method, in which both of a number of identified peptides from 6 protein standards and the less quantitative variations in the relative abundance ratios of heavy-/light-labeled corresponding peptide pairs. Finally, we applied the developed iCCM-based quantitative method to lung cancer serum proteome in order to evaluate the potential in biomarker discovery study.