• Title/Summary/Keyword: Dynamic MRM

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Dynamic MRM Measurements of Multi-Biomarker Proteins by Triple-Quadrupole Mass Spectrometry with Nanoflow HPLC-Microfluidics Chip

  • Ji, Eun-Sun;Cheon, Mi-Hee;Lee, Ju-Yeon;Yoo, Jong-Shin;Jung, Hyun-Jin;Kim, Jin-Young
    • Mass Spectrometry Letters
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    • v.1 no.1
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    • pp.21-24
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    • 2010
  • The development of clinical biomarkers involves discovery, verification, and validation. Recently, multiple reaction monitoring (MRM) coupled with stable isotope dilution mass spectrometry (IDMS) has shown considerable promise for the direct quantification of proteins in clinical samples. In particular, multiple biomarkers have been tracked in a single experiment using MRM-based MS approaches combined with liquid chromatography. We report here a highly reproducible, quantitative, and dynamic MRM system for validating multi-biomarker proteins using Nanoflow HPLC-Microfluidics Chip/Triple-Quadrupole MS. In this system, transitions were acquired only during the retention window of each eluting peptide. Transitions with the highest MRM-MS intensities for the five target peptides from colon cancer biomarker candidates were automatically selected using Optimizer software. Relative to the corresponding non-dynamic system, the dynamic MRM provided significantly improved coefficients of variation in experiments with large numbers of transitions. Linear responses were obtained with concentrations ranging from fmol to pmol for five target peptides.

The Method of Developing an Interoperation System between Multi-Resolution Models using a HLA Adapter (HLA 연동 어댑터를 사용한 다중 해상도 모델 연동체계 개발)

  • Cho, Junho;Kim, Hee-Soo;Yoo, Min-Wook
    • Journal of the Korea Institute of Military Science and Technology
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    • v.23 no.4
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    • pp.417-425
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    • 2020
  • Multi-resolution modeling(MRM) is required when simulating objects in variable resolution and can be applied for interoperating systems, which simulate objects in fixed resolution. However, most interoperation middleware do not support MRM, so participating models must handle several issues to simulate MRM system. In this paper, we propose an interoperation system, which is composed of several different resolution models, based on the High Level Architecture and Run-Time Infrastructure(HLA/RTI). In the proposed architecture, each model participates to a HLA federation through MRM adapter application, which supports data resolution conversion and HLA services while communicating with the model. MRM adapter application can be implemented based on an MRM adapter, and an adapter application development tool is proposed to support developing the application. Using the tool, developers can easily implement data resolution conversion component plugged-in HLA adapter. A case study is implemented in the proposed MRM system, and shows that models of different resolution works successfully with dynamic resolution changes.

Quantitative Analysis of Lysophosphatidic Acid in Human Plasma by Tandem Mass Spectrometry

  • Kim, Ho-Hyun;Yoon, Hye-Ran;Pyo, Dong-Jin
    • Bulletin of the Korean Chemical Society
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    • v.23 no.8
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    • pp.1139-1143
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    • 2002
  • Analysis of lysophosphatidic acids (LPAs) is of clinical importance as they can serve a potential marker for ovarian and other gynecological cancers and obesity. It is critically important to develop a highly sensitive and specific method for the early detection of gynecological cancers to improve the overall outcome of this disease. We have established a novel quantification method of LPAs in human plasma by negative ionization tandem mass spectrometry (MS-MS) using multiple reaction monitoring (MRM) mode without the conventional TLC step. Protein-bound lipids, LPAs in plasma were extracted with methanol : chloroform (2:1) containing LPA C14:0 as an internal standard under acidic condition. Following back extraction with chloroform and water, the centrifuged lower phase was evaporated and reconstituted in methanol. The reconstituted solution was directly injected into electrospray source of MS/MS. For MRM mode, Q1 ions selected were m/z 409, 433, 435, 437 and 457 which corresponds to molecular mass [M-H]- of C16:0, C18:2, C18:1, C18:0 and C20:4 LPA, respectively. Q2 ions selected for MRM were m/z 79, phosphoryl product. Using MS/MS with MRM mode, all the species of LPAs were completely separated from plasma matrix without severe interferences. This method allowed simultaneous detection and quantification of different species of LPAs in a plasma over a linear dynamic range of 0.01-25 ㎛olL-1 . The detection limit of the method was 0.3 pmol/mL, with a correlation coefficient of 0.9983 in most LPAs analyzed. When applied to the plasmas of normal and gynecological cancer patients, this new method differentiated two different groups by way of total LPA level.

Study on the Fabrication and Characterization of Hydrophobic Surface with Hierarchical Microstructure using Spray Coating Deposition Method (스프레이 코팅 증착 방식을 이용한 계층적 미세 구조의 발수표면 제작 및 특성 분석에 대한 연구)

  • Jongyun Choi;Kiwoong Kim
    • Journal of the Korean Society of Visualization
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    • v.21 no.3
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    • pp.15-22
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    • 2023
  • This research introduces an innovative approach for fabricating microstructure surfaces using spray-coating deposition. The resulting surface, referred to as Magnetically Responsive Microstructures (MRM), exhibits hierarchically structured micro-pillar arrays with remarkably high aspect ratios. The fabrication process involves precisely mixing PDMS and hexane with Carbonyl iron powders, followed by ultrasonication and spray-coating on the top of a PDMS substrate placed on the neodymium magnet. The MRM surface shows hydrophobic properties, characterized by a contact angle surpassing 150° and an aspect ratio exceeding 10. Through a comprehensive exploration of critical parameters, including spray amount, magnet-substrate distance, and solution ratio enhanced dynamic tunability and exceptional hydrophobic characteristics are attained. This novel approach holds significant potential for diverse applications in the realm of dynamically tunable microstructures and magnetically responsive surfaces.

Evaluation of storage period of fresh ginseng for quality improvement of dried and red processed varieties

  • Zhang, Na;Huang, Xin;Guo, Yun-Long;Yue, Hao;Chen, Chang-Bao;Liu, Shu-Ying
    • Journal of Ginseng Research
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    • v.46 no.2
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    • pp.290-295
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    • 2022
  • Background: Dried and red ginseng are well-known types of processed ginseng and are widely used as healthy food. The dried and red ginseng quality may vary with the storage period of raw ginseng. Therefore, herein, the effect of the storage period of fresh ginseng on processed ginseng quality was evaluated through multicomponent quantification with statistical analysis. Methods: A method based on ultrahigh performance liquid chromatography coupled to triple quadrupole mass spectrometry in multiple-reaction monitoring mode (UPLC-MRM-MS) was developed for quantitation of ginsenosides and oligosaccharides in dried and red ginseng. Principal component analysis and partial least squares discriminant analysis were conducted to evaluate the dynamic distributions of ginsenosides and oligosaccharides after different storage periods. Results: Eighteen PPD, PPT and OLE ginsenosides and nine reducing and nonreducing oligosaccharides were identified and quantified. With storage period extension, the ginsenoside content in the processed ginseng increased slightly in the first 2 weeks and decreased gradually in the following 9 weeks. The content of reducing oligosaccharides decreased continuously as storage time extending, while that of the nonreducing oligosaccharides increased. Chemical conversions occurred during storage, based on which potential chemical markers for the storage period evaluation of fresh ginseng were screened. Conclusion: According to ginsenoside and oligosaccharide distributions, it was found that the optimal storage period was 2 weeks and that the storage period of fresh ginseng should not exceed 4 weeks at 0 ℃. This study provides deep insights into the quality control of processed ginseng and comprehensive factors for storage of raw ginseng.

The Study on the Analysis Method of Tetrodotoxin in Puffer Fish (복어 중 테트로도톡신 분석법에 관한 연구)

  • Kang, Young-Woon;Lee, Yoon-Suk;Park, Sung-Kug;Seo, Jung-Heok;Kim, Mee-Hye
    • Journal of Food Hygiene and Safety
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    • v.27 no.1
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    • pp.37-41
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    • 2012
  • The current standard for testing tetrodotoxin (TTX) in foodstuffs is the mouse bioassay (MBA) in Korea as in many other countries. However, this test suffers from potential ethical concerns over the use of live animals. In addition, the mouse bioassay does not test for a specific toxin thus a sample resulting in mouse incapacitation would need further confirmatory testing to determine the exact source toxin (e.g., TTX, STX, brevotoxin, etc.). Furthermore, though the time of death is proportional to toxicity in this assay, the dynamic range for this proportional relationship is small thus many samples must be diluted and new mice be injected to yield a result that falls within the quantitative dynamic range. Therefore, in recent years, there have been many efforts in this field to develop alternative assays. High performance liquid chromatography (HPLC) coupled with mass spectrometry (MS) has been emerged as one of the most promising options. A LC-MS-MS method involves solid-phase extraction (SPE) and followed by analysis using an electrospray in the positive ionization mode and multiple reactions monitoring (MRM). To adopt LC-MS-MS method as alternative standard for testing TTX, we performed a validation study for the quantification of TTX in puffer fish. This LC-MS-MS method showed good sensitivity as limits of detection (LOD) of $0.03{\sim}0.08{\mu}g/g$ and limits of quantification (LOQ) of $0.10{\sim}0.25{\mu}g/g$. The linearity ($r^2$) of tetrodotoxin were 0.9986~0.9997, the recovery were 80.9~103.0% and the relative standard deviations (RSD) were 4.3~13.0%. The correlation coefficient between the mouse bioassay and LC/MS/MS method was higher than 0.95.

Principles and Technical Aspects of Perfusion Magnetic Resonance Imaging (관류 자기공명영상의 원리 및 기술)

  • Jahng, Geon-Ho;Kim, Ho-Sung;Kim, Sun-Mi;Ryu, Chang-Woo
    • Investigative Magnetic Resonance Imaging
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    • v.15 no.2
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    • pp.91-101
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    • 2011
  • Perfusion magnetic resonance imaging (pMRI) is a special technique for evaluation of blood flow. Exogenous pMRI methods which are dynamic susceptibility contrast (DSC) and dynamic contrast-enhanced (DCE) use an intravenous bolus injection of paramagnetic contrast agent. In contrast, an endogenous pMRM method which is arterial spin labeling (ASL) use diffusible blood in body. In order to scan pMRI in human, technical optimizations are very important according to disease conditions. For examples, DSC is popularly used in patients with acute stroke due to its short scan time, while DSC or DCE provides the various perfusion indices for patients with tumor. ASL is useful for children, women who are expected to be pregnant, and in patients with kidney diseases which are problematic in nephrogenic systemic fibrosis (NSF). Perfusion MRI does not require any injection of radioisotopes. We expect that demand for perfusion MRI will be higher in evaluating drug efficacy and other treatment effects.

Validation of the LC-MS/MS Method for Ginsenoside Rb1 Analysis in Human Plasma (LC-MS/MS를 이용한 인체 혈장에서 Ginsenoside Rb1의 분석법 검증)

  • Han, Song-Hee;Kim, Yunjeong;Jeon, Ji-Young;Hwang, Minho;Im, Yong-Jin;Lee, Sun Young;Chae, Soo-Wan;Kim, Min-Gul
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.41 no.12
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    • pp.1753-1757
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    • 2012
  • A new liquid chromatographic tandem mass spectrometric (LC-MS/MS) assay for the quantification of ginsenoside Rb1 in human plasma was developed and validated. The separation was performed on a Agilent C18 column ($4.6mm{\times}150mm$, particle size 5 ${\mu}m$) with a gradient elution of 0.1% formic acid in water and 0.1% formic acid in methanol and a flow rate of 0.9 mL/min. The analyte was determined using electrospray positive ionization mass spectrometry in the multiple reaction monitoring (MRM) mode (m/z 1131.714${\rightarrow}$365.303). Human plasma samples were extracted with acetone : water (50:50) by the liquid-liquid extraction method. The method was linear over the dynamic range of 10~500 ng/mL with a correlation coefficient of r=0.9995. The intra-and inter-day precision over the concentration range of ginsenoside Rb1 was lower than 5.8% (correlation of variance, CV), and the accuracy was between 96.0~104.6%. This LC-MS/MS assay of ginsenoside Rb1 in human plasma is applicable for quantification in a pharmacokinetic study.