Development of the quantitative measurement methods by LC-MS/MS for clinical laboratory applications.

• Project/Area Number: 15K08610
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Chiba University
• Principal Investigator: Satoh Mamoru 千葉大学, 医学部附属病院, 特任准教授 (20401002)
• Co-Investigator(Kenkyū-buntansha): 小川 祥二郎 東京理科大学, 薬学部薬学科, 講師 (30546271) ; 野村 文夫 千葉大学, 医学部附属病院, 特任教授 (80164739) ; 西村 基 千葉大学, 医学部附属病院, 講師 (80400969) ; 東 達也 東京理科大学, 薬学部薬学科, 教授 (90272963)
• Co-Investigator(Renkei-kenkyūsha): Ishige Takayuki 千葉大学, 医学部附属病院, 臨床検査技師 (30757315) ; Sangai Takafumi 千葉大学, 医学部附属病院, 助教 (00375685)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: LC-MS/MS / Vitamin D / Estrogen / 同時定量 / 臨床検査

Outline of Final Research Achievements

We have developed and validated three simultaneous measurement methods by LC-MS/MS. Target analytes are four vitamin D metabolites [25(OH)D3, 3-epi-25(OH)D3, 25(OH)D2 and 24,25(OH)2D3], two active forms of vitamin D and two estrogen (Estrone and Estradiol). Our developed methods can meet the majority of clinical needs like sensitivity, accuracy, reproducibility and throughput. Additionally, we determined the effects of various preanalytical factors such as interferences, long sample sitting prior to serum separation, repeated freeze-thaw cycles on these determinations. Various preanalytical factors had no significant effects on these determinations. These methods will aid further understanding of low-abundance analytes, as well as the accurate determination of each target analytes.

Research Products

• [Journal Article] An improved in-house lysis-filtration protocol for bacterial identification from positive blood culture bottles with high identification rates by MALDI-TOF MS. (2018)
  • Author(s): Tsuchida S, Murata S, Miyabe A, Satoh M, Takiwaki M, Matsushita K, Nomura F
  • Journal Title: Journal of microbiological methods Volume: 18 Pages: 1684-1688
  • DOI: 10.1016/j.mimet.2018.03.014
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Capsular serotyping of Haemophilus influenzae by using matrix-associated laser desorption ionization-time of flight mass?spectrometry. (2018)
  • Author(s): Takeuchi N, Segawa S, Ishiwada N, Ohkusu M, Tsuchida S, Satoh M, Matsushita K, Nomura F
  • Journal Title: Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy Volume: 18 Issue: 7 Pages: 300062-66
  • DOI: 10.1016/j.jiac.2018.02.007
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Surveillance evaluation of the standardization of assay values for serum total 25-hydroxyvitamin D concentration in Japan. (2018)
  • Author(s): Ihara H, Kiuchi S, Ishige T, Nishimura M, Matsushita K, Satoh M, Nomura F, Yamashita M, Kitajima I, Tsugawa N, Okano T, Hirota K, Miura M, Totani M, Hashizume N; Nutrition Division, Japan Society of Clinical Chemistry.
  • Journal Title: Ann Clin Biochem. Volume: Epub ahead of print Issue: 6 Pages: 0-0
  • DOI: 10.1177/0004563218765570
  • Peer Reviewed / Open Access
• [Journal Article] Assessment by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry of the Effects of Preanalytical Variables on Serum Peptidome Profiles Following Long-Term Sample Storage. (2018)
  • Author(s): Tsuchida S, Satoh M, Umemura H, Sogawa K, Takiwaki M, Ishige T, Miyabayashi Y, Iwasawa Y, Kobayashi S, Beppu M, Nishimura M, Kodera Y, Matsushita K, Nomura F
  • Journal Title: Proteomics. Clinical applications Volume: 15 Issue: 3 Pages: 47-53
  • DOI: 10.1002/prca.201700047
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] FIR haplodeficiency promotes splicing to pyruvate kinase M2 (2017)
  • Author(s): A. Kimura, K.Kitamura, M. Satoh, K. Matsushita, et al.
  • Journal Title: Oncotarget Volume: 40 Issue: 40 Pages: 67955-67965
  • DOI: 10.18632/oncotarget.19061
  • Peer Reviewed / Open Access
• [Journal Article] Improved sensitivity of serum/plasma 1α,25-dihydroxyvitamin D quantification by DAPTAD derivatization (2017)
  • Author(s): Ishige Takayuki, Satoh Mamoru, Ogawa Shoujiro, Nishimura Motoi, Matsushita Kazuyuki, Higashi Tatsuya, Nomura Fumio
  • Journal Title: Clinica Chimica Acta Volume: 473 Pages: 173-179
  • DOI: 10.1016/j.cca.2017.08.033
  • Peer Reviewed / Open Access
• [Journal Article] Ubiquitination in Periodontal Disease: A Review (2017)
  • Author(s): Tsuchida S, Satoh M, Takiwaki M, Nomura F
  • Journal Title: Int J Mol Sci Volume: 18 Issue: 7 Pages: 1476-1476
  • DOI: 10.3390/ijms18071476
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Applications of copolymer for rapid identification of bacteria in blood culture broths using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. (2017)
  • Author(s): Ashizawa K, Murata S, Terada T, Ito D, Bunya M, Watanabe K, Teruuchi Y, Tsuchida S, Satoh M, Nishimura M, Matsushita K, Sugama Y, Nomura F
  • Journal Title: Journal of microbiological methods Volume: 139 Pages: 54-60
  • DOI: 10.1016/j.mimet.2017.04.013
  • Peer Reviewed / Open Access
• [Journal Article] Immune-complex level of cofilin-1 in sera is associated with cancer progression and poor prognosis in pancreatic cancer. (2017)
  • Author(s): Satoh M, Takano S, Sogawa K, Noda K, Yoshitomi H, Ishibashi M, Mogushi K, Takizawa H, Otsuka M, Shimizu H, Miyazaki M, Nomura F.
  • Journal Title: Cancer Sci. Volume: 印刷中 Issue: 4 Pages: 795-803
  • DOI: 10.1111/cas.13181
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Dioleoyl-phosphatidic acid selectively binds to α-synuclein and strongly induces its aggregation (2017)
  • Author(s): Satoru Mizuno, Hirotaka Sasai, Aiko Kume, Mamoru Satoh, Sayaka Kado, Fumio Sakane
  • Journal Title: FEBS Letters Volume: 591 Issue: 5 Pages: 784-791
  • DOI: 10.1002/1873-3468.12592
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Enhancing analysis throughput, sensitivity and specificity in LC/ESI-MS/MS assay of plasma 25-hydroxyvitamin D3 by derivatization with triplex DAPTAD isotopologues (2017)
  • Author(s): S. Ogawa, H. Kittaka, A. Nakata, M. Satoh, F. Nomura, T. Higashi
  • Journal Title: Journal of Pharmaceutical and Biomedical Analysis Volume: 136 Pages: 126-133
  • DOI: 10.1016/j.jpba.2016.11.030
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Proteome analysis of hemofilter adsorbates to identify novel substances of sepsis: a pilot study (2017)
  • Author(s): Hashida T, Nakada TA, Satoh M, Tomita K, Kawaguchi R, Nomura F, Oda S.
  • Journal Title: J Artif Organs Volume: 20 Issue: 2 Pages: 132-137
  • DOI: 10.1007/s10047-016-0936-3
  • Peer Reviewed / Open Access
• [Journal Article] Fractionation of gamma-glutamyltransferase in patients with nonalcoholic fatty liver disease and alcoholic liver disease (2016)
  • Author(s): Sueyoshi S, Sawai S, Satoh M, Seimiya M, Sogawa K, Fukumura A, Tsutsumi M, Nomura F
  • Journal Title: World J Hepatol Volume: 8 Issue: 36 Pages: 1610-1616
  • DOI: 10.4254/wjh.v8.i36.1610
  • Peer Reviewed / Open Access
• [Journal Article] Valosin-containing Protein is a Target of 5'-l Fuligocandin B and Enhances TRAIL Resistance in Cancer Cells (2016)
  • Author(s): Arai, M. A.*; Taguchi, S.; Komatsuzaki, K.; Uchiyama, K.; Masuda, A.; Sampei, M.; Satoh, M.; Kado, S.; Ishibashi, M.*
  • Journal Title: ChemistryOPEN Volume: 5 Issue: 6 Pages: 574-579
  • DOI: 10.1002/open.201600081
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Fibrinogen alpha C chain 5.9 kDa fragment (FIC5.9), a biomarker for various pathological conditions, is produced in post-blood collection by fibrinolysis and coagulation factors (2016)
  • Author(s): Kikuchi W, Nishimura M, Kuga T, Tsuchida S, Saito T, Satoh M, Noda K, Kodera Y, Tomonaga T, Nomura F
  • Journal Title: Clinical Proteomics Volume: 13 Issue: 1 Pages: 27-27
  • DOI: 10.1186/s12014-016-9129-6
  • Peer Reviewed / Open Access
• [Journal Article] Anti-FIRs (PUF60) auto-antibodies are detected in the sera of early-stage colon cancer patients. (2016)
  • Author(s): Kobayashi S, Hoshino T, Hiwasa T, Satoh M, Rahmutulla B, Tsuchida S, Komukai Y, Tanaka T, Matsubara H, Shimada H, Nomura F, Matsushita K
  • Journal Title: Oncotarget Volume: 7 Issue: 50 Pages: 82493-82503
  • DOI: 10.18632/oncotarget.12696
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Identification of a novel serum biomarker for pancreatic cancer, C4b-binding protein α-chain (C4BPA) by quantitative proteomic analysis using tandem mass tags. (2016)
  • Author(s): Sogawa K, Takano S, Iida F, Satoh M, Tsuchida S, Kawashima Y, Yoshitomi H, Sanda A, Kodera Y, Takizawa H, Mikata R, Ohtsuka M, Shimizu H, Miyazaki M, Yokosuka O, Nomura F.
  • Journal Title: Br J Cancer. Volume: 115 Issue: 8 Pages: 949-956
  • DOI: 10.1038/bjc.2016.295
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] A Method for Simultaneous Determination of 25-Hydroxyvitamin D₃ and Its 3-Sulfate in Newborn Plasma by LC/ESI-MS/MS after Derivatization with a Proton-Affinitive Cookson-Type Reagent (2016)
  • Author(s): T. Higashi, M. Yokota, A. Goto, S. Ogawa, K. Komatsu, T. Sugiura, M. Satoｈ, F. Nomura
  • Journal Title: Mass Spectrometry Volume: 5 Issue: 2 Pages: S0051-S0051
  • DOI: 10.5702/massspectrometry.S0051
  • NAID: 130005263499
  • ISSN: 2186-5116, 2187-137X
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Development and validation of the simultaneous measurement of four vitamin D metabolites in serum by LC-MS/MS for clinical laboratory applications (2016)
  • Author(s): Mamoru Satoh, Takayuki Ishige, Shoujiro Ogawa, Motoi Nishimura, Kazuyuki Matsushita, Tatsuya Higashi, Fumio Nomura
  • Journal Title: Anal Bioanal Chem Volume: 408 Issue: 27 Pages: 7617-7627
  • DOI: 10.1007/s00216-016-9821-4
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Combined Secretomics and Transcriptomics Revealed Cancer-Derived GDF15 is Involved in Diffuse-Type Gastric Cancer Progression and Fibroblast Activation. (2016)
  • Author(s): Ishige T, Nishimura M, Satoh M, Fujimoto M, Fukuyo M, Semba T, Kado S, Tsuchida S, Sawai S, Matsushita K, Togawa A, Matsubara H, Kaneda A, Nomura F
  • Journal Title: Sci Rep. Volume: 6 Issue: 1 Pages: 21681-21681
  • DOI: 10.1038/srep21681
  • Peer Reviewed / Open Access
• [Journal Article] Alternative Splicing Detection as a Biomarker for Cancer Diagnosis: A Novel Progressive Mechanism of Acute Lymphoblastic Leukemia with Alternative Splicing as a Biomarker Candidate. (2015)
  • Author(s): Kitamura K, Matsushita K, Kobayashi S, Ishige T, Semba T, Kimura A, Kazami T, Ohyama M, Itoga S, Beppu M, Nishimura M, Satoh M, Nomura F.
  • Journal Title: Rinsho Byori. Volume: 63(9) Pages: 1091-1102
  • Peer Reviewed
• [Journal Article] Assessment of Vitamin D Metabolism by LC-MS/MS. (2015)
  • Author(s): Ishige T, Satoh M, Ogawa S, Nishimura M, Higashi T, Nomura F.
  • Journal Title: Rinsho Byori. Volume: 63(4) Pages: 457-464
  • NAID: 40020474101
  • Peer Reviewed
• [Journal Article] Autoantibodies against vinculin in patients with chronic inflammatory demyelinating polyneuropathy. (2015)
  • Author(s): Beppu M, Sawai S, Satoh M, Mori M, Kazami T, Misawa S, Shibuya K, Ishibashi M, Sogawa K, Kado S, Kodera Y, Nomura F, Kuwabara S.
  • Journal Title: J Neuroimmunol. Volume: 287 Pages: 9-15
  • DOI: 10.1016/j.jneuroim.2015.07.012
  • Peer Reviewed
• [Journal Article] Evaluation of serum carbohydrate-deficient transferrin by HPLC and MALDI-TOF MS. (2015)
  • Author(s): Sogawa K, Iida F, Kawshima Y, Yamada M, Satoh M, Sanda A, Takizawa H, Maruyama K, Wada Y, Nomura F.
  • Journal Title: Clin Chim Acta. Volume: 448 Pages: 8-12
  • DOI: 10.1016/j.cca.2015.06.005
  • Peer Reviewed
• [Journal Article] Urinary albumin and transferrin as early diagnostic markers of chronic kidney disease (2015)
  • Author(s): Maeda H, Sogawa K, Sakaguchi K, Abe S, Sagizaka W, Mochizuki S, Horie W, Watanabe T, Shibata Y, Satoh M, Sanda A, Nomura F, Suzuki J.
  • Journal Title: Journal of Veterinary Medical Science Volume: 77 Issue: 8 Pages: 937-943
  • DOI: 10.1292/jvms.14-0427
  • NAID: 130005094672
  • ISSN: 0916-7250, 1347-7439
  • Peer Reviewed / Open Access
• [Journal Article] Increased cell proliferation and differential protein expression induced by low-level Er:YAG laser irradiation in human gingival fibroblasts: proteomic analysis. (2015)
  • Author(s): Ogita M, Tsuchida S, Aoki A, Satoh M, Kado S, Sawabe M, Nanbara H, Kobayashi H, Takeuchi Y, Mizutani K, Sasaki Y, Nomura F, Izumi Y.
  • Journal Title: Lasers Med Sci. Volume: 94 Issue: 7 Pages: 555-61
  • DOI: 10.1007/s10103-014-1691-4
  • Peer Reviewed
• [Journal Article] Nuclear accumulation of annexin A2 contributes to chromosomal instability by coilin-mediated centromere damage (2015)
  • Author(s): Kazami, T., Nie, H., Satoh, M., Kuga, T., Matsushita, K., Kawasaki, N., Tomonaga, T*., and Nomura, F
  • Journal Title: Oncogene Volume: in press Issue: 32 Pages: 4177-4189
  • DOI: 10.1038/onc.2014.345
  • Peer Reviewed
• [Presentation] 臨床検査室導入に向けた質量分析の役割と問題点～ビタミンD測定を中心に～ (2017)
  • Author(s): 佐藤 守、野村文夫
  • Organizer: 第65回質量分析総合討論会
  • Invited
• [Presentation] LC-MS を用いた定量解析 (2017)
  • Author(s): 佐藤 守
  • Organizer: 日本医用マススペクトル学会 第2回東部会
  • Invited
• [Presentation] The role of mass spectrometry in clinical laboratory: focusing on vitamin D testing. (2016)
  • Author(s): Mamoru Satoh
  • Organizer: The 32nd World Congress of Biomedical Laboratory Science - IFBLS 2016
  • Place of Presentation: 神戸国際会議場（兵庫県・神戸市）
  • Year and Date: 2016-08-31
  • Int'l Joint Research / Invited
• [Presentation] Development and validation of simultaneous measurements of four vitamin D metabolites in serum by LC-MS/MS for Clinical laboratory (2016)
  • Author(s): Satoh M, Ishige T, Ogawa S, Nishimura M, Matsushita K, Higashi T, Nomura F.
  • Organizer: The Official 68th AACC Annual Scientific Meeting & Clinical Lab Expo
  • Place of Presentation: Philadelphia（アメリカ）
  • Year and Date: 2016-07-31
  • Int'l Joint Research
• [Presentation] Analytical and preanalytical validation of simultaneous measurements of estrone and 17b-estradiol in serum by LC-MS/MS (2016)
  • Author(s): Miyabayashi Y, Satoh M, Takiwaki M, Nishimura M, Matsushita K, Shozu M, Nomura F
  • Organizer: The Official 68th AACC Annual Scientific Meeting & Clinical Lab Expo
  • Place of Presentation: Philadelphia（アメリカ）
  • Year and Date: 2016-07-31
  • Int'l Joint Research
• [Presentation] The role of mass spectrometry in clinical laboratory: focusing on vitamin D testing (2015)
  • Author(s): Mamoru Satoh
  • Organizer: World Association of Societies of Pathology and Laboratory Medicine
  • Place of Presentation: Cancun, Mexico
  • Year and Date: 2015-11-20
  • Int'l Joint Research / Invited
• [Presentation] LC/MS/MSの臨床検査応用 ービタミンD代謝物測定を基盤にー (2015)
  • Author(s): 佐藤 守
  • Organizer: 日本臨床検査自動化学会 第47回大会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2015-10-10
• [Presentation] LC/MS/MS の臨床検査応用への取り組み (2015)
  • Author(s): 佐藤 守
  • Organizer: 第 40回 日本医用マススペクトル学会年会
  • Place of Presentation: アクトシティ浜松 コングレスセンター（静岡県浜松市）
  • Year and Date: 2015-09-17
  • Invited
• [Presentation] LC/MS/MSの臨床検査応用 ―ビタミンD代謝物測定を基盤に― (2015)
  • Author(s): 佐藤 守, 石毛崇之, 小川祥二郎, 西村 基, 松下一之, 東 達也, 野村文夫
  • Organizer: 第 40回 日本医用マススペクトル学会年会
  • Place of Presentation: アクトシティ浜松 コングレスセンター（静岡県浜松市）
  • Year and Date: 2015-09-16
• [Presentation] Effects of preanalytical variables on serum peptidome profiling for long-term storage using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (2015)
  • Author(s): 土田祥央, 佐藤 守, 梅村啓史, 曽川一幸, 滝脇正貴, 別府美奈子, 西村 基, 小寺義男, 松下一之, 野村文夫
  • Organizer: 第 40回 日本医用マススペクトル学会年会
  • Place of Presentation: アクトシティ浜松 コングレスセンター（静岡県浜松市）
  • Year and Date: 2015-09-16
• [Presentation] LC-MS/MSによる血清エストロゲンおよびプロゲステロンの同時定量 (2015)
  • Author(s): 宮林佑衣, 佐藤 守, 滝脇正貴, 西村 基, 松下一之, 野村文夫
  • Organizer: 第 40回 日本医用マススペクトル学会年会
  • Place of Presentation: アクトシティ浜松 コングレスセンター（静岡県浜松市）
  • Year and Date: 2015-09-16
• [Presentation] LC/MS/MSの臨床検査応用への取り組み (2015)
  • Author(s): 佐藤 守
  • Organizer: サーモフィッシャーサイエンティフィック株式会社 研究開発者交流のための機器分析ユーザーズフォーラム2015
  • Place of Presentation: ホテル阪急インターナショナル（大阪府大阪市）
  • Year and Date: 2015-07-29
  • Invited
• [Presentation] LC/MS/MS の臨床検査応用 ― ビタミン D 代謝物測定を基盤に ― (2015)
  • Author(s): 佐藤 守, 石毛崇之, 小川祥二郎, 西村 基, 松下一之, 東 達也, 野村文夫
  • Organizer: JHUPO 第13回大会
  • Place of Presentation: くまもと森都心プラザ（熊本県熊本市）
  • Year and Date: 2015-07-13
• [Remarks] マススペクトロメトリー検査診断学
  • URL: http://www.ho.chiba-u.ac.jp/Clinical_MS/index.html