Journal of the Mass Spectrometry Society of Japan
Online ISSN : 1880-4225
Print ISSN : 1340-8097
ISSN-L : 1340-8097
56 巻, 3 号
選択された号の論文の13件中1~13を表示しています
一般論文
  • Naofumi HOSOKAWA, Yuki SUGIURA, Mitsutoshi SETOU
    2008 年 56 巻 3 号 p. 77-81
    発行日: 2008/06/01
    公開日: 2008/06/21
    ジャーナル フリー
    In this study, we aimed at establishing a procedure for normalizing mass spectra to improve ion distribution images, i.e., sharply defined tissue edges and increased dynamic range, acquired by mass spectrometric imaging (MSI). A crucial problem in MSI is that variations in ionization efficiencies are observed among spectra, which arises from the heterogeneous matrix-analyte crystallization and sublimation during measurement. Such variation could generate incorrect analyte distribution images. For solving this problem, we performed spectrum normalization using an external standard (ES) compound spiked in the matrix solution. We selected methylcarbamyl platelet-activating factor (C-PAF) (C-16) as the ES compound by considering the following two criteria: (1) no other mass peaks overlap the peak of the ES compound, and (2) the ES compound has sufficient ionization capability on the tissue section, in which numerous biological compounds compete to ionize. For evaluating the optimal concentration of C-PAF, we analyzed ion images of coronal mouse brain sections by MSI using matrix solutions containing different concentrations of C-PAF (0, 0.5, 5, 25, and 50 μg/mL). As a result, we found that the optimal concentration of C-PAF for normalization is 50 μg/mL. Employing the procedure, we show improved ion images of phosphatidylcholine (PC) molecular species in the mouse brain section.
総説
  • 寺本 華奈江, 佐藤 浩昭
    2008 年 56 巻 3 号 p. 83-90
    発行日: 2008/06/01
    公開日: 2008/06/21
    ジャーナル フリー
    Rapid identification and classification of bacteria by mass spectrometry (MS) have been expected to play important roles in various fields such as food industries, biomedical assays, and environmental analysis. In this review, the historical progress of various mass spectrometric approaches from pyrolysis-MS to matrix-assisted laser desorption/ionization (MALDI)-MS and their features are outlined. Then, the details of the development of bacterial analysis based on MALDI-MS are discussed. Among these, recent progress in MALDI-MS-based identification and classification of bacteria using ribosomal proteins as biomarkers is described in brief.
  • 瀬戸 康雄, 金森 美江子, 柘 浩一郎
    2008 年 56 巻 3 号 p. 91-115
    発行日: 2008/06/01
    公開日: 2008/06/21
    ジャーナル フリー
    The Tokyo subway sarin gas attack in 1995 and the US postal anthrax letter attack in 2001 presented a threat of chemical and biological terrorism all over the world. To realize safe and secure society, the authority should establish a more strengthened crisis management system at national level for civil defense. Detection and identification of the causative agents is very important for countering chemical and biological terrorism from the standpoint of damage minimization. Various kinds of measuring technologies have been used for the on-site detection and laboratory identification of chemical and biological warfare agents (CBWAs). This review highlights the physicochemical and toxic properties of CBWAs, detection and identification requirements for crisis management, and the present status of detection technologies. Efficiency of mass spectrometry is compared with that of other analytical technologies from the standpoint of countering chemical and biological terrorism.
解説
  • 三井 利幸
    2008 年 56 巻 3 号 p. 117-122
    発行日: 2008/06/01
    公開日: 2008/06/21
    ジャーナル フリー
    Quantitative analysis of components in a sample can be performed by the different calculation method of regression analysis (DCR) without a calibration curve or separation of the components. In addition, the mixing ratio of different components in an unknown sample is determined from a multiple regression equation obtained using the measured values of two or more known samples and the unknown sample. In the present study, the mixing ratio of air and organic solvent vapors in an unknown sample was determined from the mass fragment values of several known samples and air measured with a gas chromatograph-mass spectrometer by DCR. Using this method, the mixing ratio of an unknown sample was determined without interference from other substances that might be present in the sample. Furthermore, the existence of a small unrecognized component in an unknown sample was deduced based on the difference between the measured and calculated values.
  • 工藤 恵子, 石田 知己, 池田 典昭
    2008 年 56 巻 3 号 p. 123-130
    発行日: 2008/06/01
    公開日: 2008/06/21
    ジャーナル フリー
    In this paper, we describe our approach to developing a systematic screening procedure for abused drugs that does not require the use of standard compounds. This procedure uses gas chromatography/mass spectrometry (GC/MS) with retention time locking. Fifty-five abused drugs, including amphetamine, piperazine, tryptamine and phenetylamine derivatives, opiates, and benzodiazepines, were selected as target compounds. The method consists of solid-phase extraction with a polar-enhanced FocusTM column followed by acetylation and GC/MS with retention time locking. Based on this method, an “abused drugs database,” which includes the retention time, qualifier ion/target ion percentage, and calibration curve (values of slope and intercept), was constructed using the novel GC/MS software, NAGINATATM. Using this database, we found a significant improvement in the data analysis time, and qualitative and quantitative information about each drug was obtained without using standard compounds. The practical applications for examining urine samples in forensic cases are also presented.
  • 石井 晃, 金子 理奈, 平田 ゆかり, 浜島 誠
    2008 年 56 巻 3 号 p. 131-138
    発行日: 2008/06/01
    公開日: 2008/06/21
    ジャーナル フリー
    In the fields of legal medicine and forensic toxicology, numerous drugs and poisons obtained from diverse biological specimens such as whole blood, urine, and hair need to be identified and quantified. Therefore, it is necessary to develop new methods for analysis of drugs, especially mass spectrometric methods. In this paper, we introduce three methods—surface ionization organic mass spectrometry, a combination of mass spectrometry and cryogenic oven trapping (COT), and laser spray ionization (LSI)—and their application to legal medicine. Gas chromatography/surface ionization organic mass spectrometry is very sensitive in detecting drugs containing tertiary amine residues; for Phencyclidine (PCP), its sensitivity is 20 to 1,000 times higher than that of the conventional electron ionization method. Surface ionization organic mass spectrometry is suitable for compounds containing cyclic tertiary amino side chains. COT in combination with gas chromatography has enabled detection of many volatile organic compounds (VOCs) with high sensitivity. We have succeeded in quantifying several VOCs, such as chloroform, cyanide, thinner components, ethanol, and general anesthetics in whole blood by COT; COT affords a sensitivity that is 10 to 50 times higher than that of the conventional headspace gas chromatography method. Recently, we succeeded in identifying and quantifying 15 VOCs in human whole blood with the combination of COT and mass spectrometry. LSI is a new ionization method for liquid chromatography/mass spectrometry. We have succeeded in detecting aconitine alkaloids and psychopharmaceuticals using LSI. In the infusion mode, aconitine and haloperidol were ionized with higher efficiency compared to that in the conventional electrospray mode. However, since the signals in the LSI mode are not stable, it is necessary to improve the stability of signals in the LSI mode for applying LSI to forensic toxicology.
  • 岩崎 一秀
    2008 年 56 巻 3 号 p. 139-142
    発行日: 2008/06/01
    公開日: 2008/06/21
    ジャーナル フリー
    Although the expenditure for new drug development by the pharmaceutical industry has been increasing in recent years, the number of new drugs approved has remained unchanged or has been gradually decreasing. For the effective development of new drugs, attrition rates of drug candidates should be reduced. In 1991, major causes of the attrition were ADME (absorption, distribution, metabolism and excretion) (about 40%), efficacy (about 30%), and safety issues (about 25%). In 2000, the causes were ADME (less than 10%), efficacy (about 30%), and safety issues (about 30%). Between 1991 and 2000, the attrition caused by ADME issues decreased drastically, but that caused by efficacy and safety issues did not change. To improve this situation, exploratory clinical studies including microdose and exploratory IND (Investigational New Drug) studies proposed in EU and USA, respectively, have been started at the late 1990s and the early 2000s. This commentary reviews the current situation of the exploratory clinical studies and the recent trend of pharmacokinetic studies in new drug development.
  • 山本 利憲
    2008 年 56 巻 3 号 p. 143-149
    発行日: 2008/06/01
    公開日: 2008/06/21
    ジャーナル フリー
    Recent advances in drug discovery technologies require a paradigm shift in safety evaluation of drug candidates, especially with respect to their toxicological contribution at the early stage of drug discovery. In this context, new sciences and technologies should be implemented in the field of safety evaluation, and the numerous applications of mass spectrometry (MS) are thought to be one of the key approaches. In the present review, we have summarized the usability of MS and its practical applications in early safety evaluation.
  • 村井 孝弘
    2008 年 56 巻 3 号 p. 151-154
    発行日: 2008/06/01
    公開日: 2008/06/21
    ジャーナル フリー
    A large number of electrophilic reactive metabolites, such as quinone derivatives, Michael acceptors, nitrogen-containing electrophiles, and epoxides, are produced from drug candidates by drug-metabolizing enzymes, mainly cytochrome P450s. However, reactive metabolites are very unstable and can only be detected after being trapped by nucleophiles. Glutathione and its derivatives are the most utilized nucleophilic trapping reagents. Glutathione-trapped reactive metabolites can be detected by various methods using liquid chromatography-mass spectrometry. Moreover, some drug compounds are naturally chemically reactive to a certain extent. These include β-lactam antibiotics and sulfhydryl-containing drugs. Our study on rofecoxib, a cyclooxygenase-2 inhibitor withdrawn from the market in 2004, suggests that it is a nucleophilic reactive drug that reacts with the aldehyde group of allysine, thereby preventing the formation of cross-linkages in elastin and causing degradation of the elastic fibers in the aorta.
  • 明石 知子, 史 向国, 高見澤 淳, 西村 善文, 平岡 賢三
    2008 年 56 巻 3 号 p. 155-161
    発行日: 2008/06/01
    公開日: 2008/06/21
    ジャーナル フリー
    This commentary describes the advantages of laser spray, which was developed by Hiraoka et al., in the analysis of binding affinities of biomolecular complexes, such as DNA-protein and DNA-drug complexes. Since laser spray enables dissociation of the complexes without fragmentation of labile compounds such as DNA, a good correlation was found between the binding affinities and applied laser power for dissociation. We found that laser spray is promising for rapid characterization of binding affinities of complexes with small differences in structure.
  • 平山 和雄
    2008 年 56 巻 3 号 p. 163-171
    発行日: 2008/06/01
    公開日: 2008/06/21
    ジャーナル フリー
    Recently, rapid developments in mass spectrometry have enabled people who do not have adequate knowledge of chemistry to operate mass spectrometers. In addition, some sales engineers dealing with mass spectrometers have little knowledge of chemistry because they did not major in chemistry, when in university. However, basic knowledge of chemistry and mass spectrometry is necessary to obtain optimum results and to highlight the favorable points of their instruments. In this paper, we present some basic knowledge of chemistry and mass spectrometry as a short tutorial course for the abovementioned persons.
  • 吉野 健一
    2008 年 56 巻 3 号 p. 173-178
    発行日: 2008/06/01
    公開日: 2008/06/21
    ジャーナル フリー
    Some of mass spectrometrists refer to a term “mass number” as physical quantities of mass value and m/z value. However, the term “mass number” is defined as the sum of the total number of protons and neutrons in an atomic nucleus, atom, molecule, ion, or radical.
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