Highly accurate medical therapy management by universal TDM and global metabolomics

2013 Fiscal Year Final Research Report

• Project/Area Number: 24659012
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Physical pharmacy
• Research Institution: Tohoku University
• Principal Investigator: MANO NARIYASU 東北大学, 大学病院, 教授 (50323035)
• Co-Investigator(Kenkyū-buntansha): SHIMADA Miki 鳥取大学, 医学部附属病院, 教授 (10196488)
• Co-Investigator(Renkei-kenkyūsha): MAEKAWA Masamitsu 東北大学, 病院, 助手 (70572882)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: TDM / 一斉分析

Research Abstract

We investigated linearities of phenytoin as a model drug by peak intensity plot of stable isotopes, and found saturation more than 10 thousand-fold and difference of slopes of each stable isotope line. Plotting peak area ratios using an internal standard broadens linearity range to 100 thousand-fold, and equalized approximately slopes. However, obtained results suggested that the saturation of peak intensities was caused by the saturation of ionization. Therefore, expansion of measurement range by using peak intensities of stable isotopes was limited to 100 thousand-fold. By the above results we developed a simultaneous determination method of all drugs and their metabolites used in a cancer chemotherapy regimen.

Research Products

• [Journal Article] Tandem mass spectrometric characterization of bile acids and steroid conjugates based on low-energy collision-induced dissociation (2014)
  • Author(s): Masamitsu Maekawa, Miki Shimada, Takashi Iida, Junichi Goto, and Nariyasu Mano
  • Journal Title: Steroids Volume: 80 Pages: 80-91
  • DOI: 10.1016/j.steroids.2013
  • Peer Reviewed
• [Journal Article] Influence of the meal and genotype of CYP2C19 on the pharmacokinetics of proton pump inhibitors in healthy Japanese subjects. Pharmacol (2013)
  • Author(s): Hirohiko Shinkai, Tomoyuki Koike, Miki Shimada, Kenichiro Nakagawa, Katsunori Iijima, Yotaro Matsumoto, Masamitsu Maekawa, Nariyasu Mano, and Tooru Shimosegawa
  • Journal Title: Pharm Volume: 4 Pages: 502-509
  • DOI: 10.4236/pp.2013.46073
  • Peer Reviewed
• [Journal Article] An efficient synthesis of 4α- and 4β-hydroxy-7-dehydrocholesterol, biomarkers for patients with and animal models of the Smith-Lemli-Opitz syndrome (2013)
  • Author(s): Hiroaki Kawamoto, Yuusuke Ohmori, Masamitsu Maekawa, Mki Shimada, Nariyasu Mano, and Takashi Iida
  • Journal Title: Chem. Phys. Lipids Pages: 175-176, 73-78
  • DOI: 10.1016/j.chemphyslip.2013.07.004
  • Peer Reviewed
• [Journal Article] LC/ESI-MS/MS analysis of urinary 3β-sulfooxy-7β-N-acetylglucosaminyl-5-cho len-24-oic acid and its amides : new biomarkers for the detection of Niemann-Pick type C disease (2013)
  • Author(s): Masamitsu Maekawa, Yasushi Misawa, Ayako Sotoura, Hiroaki Yamaguchi, Masami Togawa, Kousaku Ohno, Hiroshi Nittono, Genta Kakiyama, Takashi Iida, Alan F. Hofmann, Junichi Goto, Miki Shimada, and Nariyasu Mano
  • Journal Title: Steroids Volume: 78 Pages: 967-972
  • DOI: 10.1016/j.steroids.2013.05.017
  • Peer Reviewed
• [Journal Article] Quantification of intact carboplatin in human plasma ultrafiltrates using hydrophilic interaction liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic study (2013)
  • Author(s): Hajime Ito, Hiroaki Yamaguchi, Asuka Fujiwara, Narumi Shiida, Nobuaki Tanaka, Jiro Ogura, Masaki Kobayashi, Takehiro Yamada, Nariyasu Mano, and Ken Iseki
  • Journal Title: J. Chromatogr. B Pages: 917-918, 18-23
  • DOI: 10.1016/j.jchromb.2012.11.024
  • Peer Reviewed
• [Journal Article] Associations between visit-to-visit variability in blood pressure measured in the office and antihypertensive drugs : the J-HOME-Morning Study (2013)
  • Author(s): Taku Obara, Masahiro Kikuya, Yuka Kobayashi, Kazuki Ishikura, Urara Ikeda, Mami Ishikuro, Hirohito Metoki, Nariyasu Mano, Shinichi Kuriyama, Takayoshi Ohkubo, Yutaka Imai, and the J-HOME-Morning Study Group
  • Journal Title: Clin. Exp. Hypertens Volume: 35 Pages: 285-290
  • DOI: 10.3109/10641963.2013.780070
  • Peer Reviewed
• [Journal Article] Change of the management of treated hypertensive patients with or without diabetes in Japan (2013)
  • Author(s): Taku Obara, Takayoshi Ohkubo, Kazuki Ishikura, Taku Shibamiya, Urara Ikeda, Hirohito Metoki, Masahiro Kikuya, Nariyasu Mano, Shinichi Kuriyama, Yutaka Imai, J-HOME Study Group, and J-HOME-Morning Study Group
  • Journal Title: Clin. Exp. Hypertens Volume: 35 Pages: 79-86
  • DOI: 10.3109/10641963.2012.732640
  • Peer Reviewed
• [Journal Article] Compliance to the recommendations on blood pressure measurements in the clinical settings (2013)
  • Author(s): Taku Obara, Takayoshi Ohkubo, Nariyasu Mano, Shinichi Kuriyama, Yutaka Imai
  • Journal Title: J. Hypertens Volume: 31 Pages: 213
  • DOI: 10.1097/HJH.0b013e32835aaffd
  • Peer Reviewed
• [Journal Article] Quantitative determination of paclitaxel and its metabolites, 6α-hydroxypaclitaxel and p-3'-hydroxypaclitaxel, in human plasma using column-switching liquid chromatography/tandem mass spectrometry (2013)
  • Author(s): Hiroaki Yamaguchi, Asuka Fujiwara, Hajime Ito, Nobuaki Tanaka, Ayako Furugen, Kazuaki Miyamori, Natsuko Takahashi, Jiro Ogura, Masaki Kobayashi, Takehiro Yamada, Nariyasu Mano, and Ken Iseki
  • Journal Title: Biomed. Chromatogr Volume: 27 Pages: 539-544
  • DOI: 10.1002/bmc.2826
  • Peer Reviewed
• [Journal Article] Increased production of reactive oxygen species by the vacuolar-type (H^+)-ATPase inhibitors bafilomycin A1 and concanamycin A in Raw 264 cells (2012)
  • Author(s): Aya Yokomakura, JangJa Hong, Kazuo Ohuchi, Seong-Eun Oh, Jin-Yong Lee, Nariyasu Mano, Tsutomu Takahashi, Gi-Wook Hwang, and Akira Naganuma
  • Journal Title: J. Toxicol. Sci Volume: 37 Pages: 1045-1048
  • DOI: 10.2131/jts.37.1045
  • Peer Reviewed
• [Journal Article] A full validated hydrophilic interaction liquid chromatography?tandem mass spectrometric method for the quantification of oxaliplatin in human plasma ultrafiltrates (2012)
  • Author(s): Hajime Ito, Hiroaki Yamaguchi, Asuka Fujiwara, Nobuaki Tanaka, Ayako Furugen, Kazuaki Miyamori, Natsuko Takahashi, Jiro Ogura, Masaki Kobayashi, Takehiro Yamada, Nariyasu Mano, and Ken Iseki
  • Journal Title: J. Pharm. Biomed. Anal Volume: 71 Pages: 99-103
  • DOI: 10.1016/j/jpba.2012.08.010
  • Peer Reviewed
• [Journal Article] Simultaneous quantification of sphingoid bases and their phosphates in biological samples by liquid chromatography/electrospray ionization tandem mass spectrometry (2012)
  • Author(s): Daisuke Saigusa, Kanako Shiba, Asuka Inoue, Kotaro Hama, Michiyo Okutani, Nagisa Iida, Masayoshi Saito, Kaori Suzuki, Tohru Kaneko, Naoto Suzuki, Hiroaki Yamaguchi, Nariyasu Mano, Junichi Goto, Takanori Hishinuma, Junken Aoki, and Yoshihisa Tomioka
  • Journal Title: Anal. Bioanal. Chem Volume: 403 Pages: 1897-1905
  • DOI: 10.1007/s00216-012-6004-9
  • Peer Reviewed
• [Journal Article] A rapid and sensitive LC/ESI-MS/MS method for quantitative analysis of docetaxel in human plasma and its application to a pharmacokinetic study (2012)
  • Author(s): Hiroaki Yamaguchi, Asuka Fujiwara, Hajime Ito, Nobuaki Tanaka, Ayako Furugen, Kazuaki Miyamori, Natsuko Takahashi, Jiro Ogura, Masaki Kobayashi, Takehiro Yamada, Nariyasu Mano, and Ken Iseki
  • Journal Title: J. Chromatogr. B Pages: 893-894, 157-161
  • DOI: 10.1016/j/jchromb.2012.02.003
  • Peer Reviewed
• [Journal Article] DCK is frequently inactivated in acquired gemcitabine-resistant human cancer cells (2012)
  • Author(s): Yuriko Saiki, Yuki Yoshino, Hiroko Fujimura, Tatsuya Manabe, Yuki Kudo, Miki Shimada, Nariyasu Mano, Tomohiro Nakano, Yoonha Lee, Shinjiro Shimizu, Shinya Oba, Sho Fujiwara, Hideyuki Shimizu, Na Chen, Zhaleh K Nezhad, Guo Jin, Shinichi Fukushige, Makoto Sunamura, Masaharu Ishida, Fuyuhiko Motoi, Shinichi Egawa, Michiaki Unno, and Akira Horii
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 421 Pages: 98-104
  • DOI: 10.1016/j.bbrc.2013.03.122
  • Peer Reviewed
• [Journal Article] Pharmacists'awareness and attitude toward blood pressure measurement at home and in the pharmacy in Japan (2012)
  • Author(s): Taku Obara, Takayoshi Ohkubo, Koji Tanaka, Michihiro Satoh, Kazuki Ishikura, Mitsuru Kobayashi, Hirohito Metoki, Kei Asayama, Masahiro Kikuya, Yuriko Murai, Nariyasu Mano, Sentaro Oide, and Yutaka Imai
  • Journal Title: Clin. Exp. Hypertens Volume: 34 Pages: 447-455
  • DOI: 10.3109/10641963.2012.666599
  • Peer Reviewed
• [Journal Article] Associations between day-by-day variability in blood pressure measured at home and antihypertensive drugs : the J-HOME-Morning Study (2012)
  • Author(s): Kazuki Ishikura, Taku Obara, Tetsuo Kato, Masahiro Kikuya, Taku Shibamiya, Takahiro Shinki, Urara Ikeda, Yuka Kobayashi, Hirohito Metoki, Nariyasu Mano, Shinichi Kuriyama, Takayoshi Ohkubo, Yutaka Imai, and the J-HOME-Morning Study Group
  • Journal Title: Clin. Exp. Hypertens Volume: 34 Pages: 297-304
  • DOI: 10.3109/10641963.2012.681087
  • Peer Reviewed
• [Journal Article] 特集災害医療と被害管理3.被災地の災害医療支援 (2012)
  • Author(s): 眞野成康
  • Journal Title: 医薬ジャーナル Volume: 48巻 Pages: 653-658
  • URL: https://www.iyaku-j.com/
• [Journal Article] 連載薬剤師による処方設計<11>脳死肺移植患者に対する薬学的介入と処方設支援 (2012)
  • Author(s): 土屋雅美、眞野成康
  • Journal Title: 医薬ジャーナル Volume: 48巻 Pages: 2015-2019
  • URL: https://www.iyaku-j.com/
• [Presentation] 質量分析の基礎知識と使い分け、定量分析の注意点・落とし穴(自験例提示) (2013)
  • Author(s): 眞野成康
  • Organizer: 第60回日本臨床検査医学会学術集会
  • Place of Presentation: 神戸
  • Year and Date: 20131031-1103
• [Presentation] 肝細胞癌患者におけるソラフェニブ投与に伴う副作用発現と薬物動態学的因子の関連 (2013)
  • Author(s): 島田美樹、大川星美、前嶋隆弘、近藤泰輝、下瀬川徹、久道周彦、松浦正樹、眞野成康
  • Organizer: 第51回日本癌治療学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 20131024-26
• [Presentation] Pharmacokinetics of sorafenib correlates with adverse effects upon dosage reduction or withdrawal in patients with hepatocellular carcinoma (2013)
  • Author(s): Miki Shimada, Hoshimi Okawa, Takahiro Maejima, Yasuteru Kondo, Tooru Shimosegawa, Kanehiko Hisamichi, Masaki Matsuura, and Nariyasu Mano
  • Organizer: 10th International Society of Study of Xenobiotica
  • Place of Presentation: Tront, Canada
  • Year and Date: 20130929-1003
• [Presentation] 同種臍帯血移植直後にボリコナゾールの血中濃度が低下した一症例 (2013)
  • Author(s): 鈴木裕之、北村奈央子、柳利樹、相馬真志、佐藤祐司、前川正充、石澤賢一、張替秀郎、島田美樹、眞野成康
  • Organizer: 第23回日本医療薬学会年会
  • Place of Presentation: 仙台
  • Year and Date: 20130921-22
• [Presentation] LC/ESI-MS/MSによる患者血清中のパクリタキセル及び代謝物とカルボプラチンの同時測定法 (2013)
  • Author(s): 中村昌由、鈴木裕之、森大、内田敬、前川正充、島田美樹、眞野成康
  • Organizer: 第23回日本医療薬学会年会
  • Place of Presentation: 仙台
  • Year and Date: 20130921-22
• [Presentation] がん化学療法レジメンで用いられる薬物の血中濃度一斉分析法 (2013)
  • Author(s): 庄司依莉子、前川正充、森大、鈴木裕之、島田美樹、眞野成康
  • Organizer: 第23回日本医療薬学会年会
  • Place of Presentation: 仙台
  • Year and Date: 20130921-22
• [Presentation] 肝細胞がん患者においてsodium alginateによりsorafenibの吸収阻害が示唆された1例 (2013)
  • Author(s): 片岡佑太、久道周彦、近藤泰輝、松浦正樹、田坂英久、下瀬川徹、島田美樹、眞野成康
  • Organizer: 第23回日本医療薬学会年会
  • Place of Presentation: 仙台
  • Year and Date: 20130921-22
• [Presentation] がん化学療法に関する薬薬医連携セミナーの開催とその効果 (2013)
  • Author(s): 菊地正史、木皿重樹、松浦正樹、久道周彦、我妻恭行、山田卓郎、加藤俊介、石岡千加史、佐々木孝雄、眞野成康
  • Organizer: 第11回日本臨床腫瘍学会学術集会
  • Place of Presentation: 仙台
  • Year and Date: 20130829-31
• [Presentation] 経口薬併用がん化学療法における地域連携への取り組み (2013)
  • Author(s): 木皿重樹、眞野成康
  • Organizer: 医療薬学フォーラム2013第21回クリニカルファーマシーシンポジウム
  • Place of Presentation: 金沢
  • Year and Date: 20130820-21
• [Presentation] LC/MS/MSによる抗がん薬の治療薬物モニタリング (2013)
  • Author(s): 島田美樹、前川正充、眞野成康
  • Organizer: 第26回バイオメディカル分析科学シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 20130802-03
• [Presentation] UHPLC-UVを用いるエルロチニブ及び代謝物の血中濃度測定法の構築 (2013)
  • Author(s): 須賀隆浩、前川正充、森大、鈴木裕之、島田美樹、眞野成康
  • Organizer: 第26回バイオメディカル分析科学シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 20130802-03
• [Presentation] 米国ノバサウスイースタン大学薬学部のカリキュラムの経験とその考察 (2013)
  • Author(s): 中川直人、Leame LAI、村井ユリ子、眞野成康
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: 横浜
  • Year and Date: 20130328-30
• [Presentation] 腎機能の低下した肝細胞癌患者における血中Sorafenib濃度の推移 (2013)
  • Author(s): 前嶋隆弘、大川星美、近藤泰輝、久道周彦、松浦正樹、下瀬川徹、島田美樹、眞野成康
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: 横浜
  • Year and Date: 20130328-30
• [Presentation] 血中濃度モニタリングを基にした分子標的薬処方設計支援 (2013)
  • Author(s): 島田美樹、眞野成康
  • Organizer: 第24回日本臨床化学会東北支部総会シンポジウム
  • Place of Presentation: 仙台
  • Year and Date: 2013-07-20
• [Presentation] 小児のセフジトレンピボキシル長期服用に伴う低血糖の回避を目的とした尿中カルニチン、アシルカルニチン及びセフジトレン同時分析法 (2013)
  • Author(s): 鈴木裕之、阿部一樹、前川正充、島田美樹、眞野成康
  • Organizer: 第24回日本臨床化学会東北支部総会
  • Place of Presentation: 仙台
  • Year and Date: 2013-07-20
• [Presentation] 治療薬物モニタリングにおける質量分析法の活用 (2012)
  • Author(s): 島田美樹、眞野成康
  • Organizer: 第59回日本臨床検査医学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 20121129-1202
• [Book] 5.5.低分子結合タンパク質解析法,第5章機能解析法,タンパク質分析 (2012)
  • Author(s): 森大、眞野成康
  • Total Pages: 291(207-218)
  • Publisher: 丸善出版