教員紹介

山下 幸和
Yamashita Kouwa

所属・肩書

漢方薬学科/薬品分析学研究室(特任教授)

最終学歴

東北大学大学院薬学研究科博士前期課程修了(薬品分析化学専攻)

取得学位

薬学博士(東北大学)

所属学会

日本薬学会、日本分析化学会、日本質量分析学会、日本薬物動態学会、American Chemical Society (ACS)、
American Society for Mass Spectrometry (ASMS)、American Association for Clinical Chemistry (AACC)

現在の専門分野

分析化学、臨床化学、機器分析学(質量分析)、リピドミクス

現在の研究課題

●質量分析法によるステロイドミクス研究
●GC-MS、LC-MSによる医薬品・生体内成分(ステロイド、プロスタノイド)の微量分析のための誘導体開発

主要研究業績

●新規シリル化剤の開発とステロイド、プロスタノイド分析への応用
●プロトン親和性誘導体の開発とステロイドの微量定量への応用
●LC-MS/MS法による微小酵素活性の測定法開発(3β-HSD、CYP17、CYP19など)
●アロマターゼの機能解析と阻害剤の開発

最近の研究業績

(2000年以降の原著論文)
1.Satoh F, Morimoto R, Ono Y, Iwakura Y, Omata K, Kudo M, Takase K, Seiji K, Sasamoto H, Honma S, Okuyama M, Yamashita K, Gomez-Sanchez CE, Rainey WE, Arai Y, Sasano H, Nakamura Y, Ito S. Measurement of Peripheral Plasma 18-Oxocortisol Can Discriminate Unilateral Adenoma From Bilateral Diseases in Patients With Primary Aldosteronism. Hypertension 2015; Mar 16: Epub ahead of print PMID 2577607.

2.Kinoshita T, Honma S, Shibata Y, Yamashita K, Watanabe Y, Maekubo H, Okuyama M, Takashima A, Takeshita N. An innovative LC-MS/MS-based method for determining CYP 17 and CYP 19 activity in the adipose tissue of pre- and postmenopausal and ovariectomized women using 13C-labeled steroid substrates. J. Clin. Endocrinol. Metab., 99, 1339-1347 (2014).

3.Asai T, Otsuki S, Taniguchi T, Monde K,Yamashita K, Sakurai H, Ozeki T, Oshima Y. Structures and absolute configurations of short-branched fatty acid dimers from an endophytic fungus of Aloe arborescens. Tetrahedron Lett., 54 (26), 3402-3405 (2014).

4.Asai T, Otsuki S, Sakurai H, Yamashita K, Ozeki T, Oshima Y. Benzophenones from an endophytic fungus, Graphiopsis chlorocephala, from Paeonia lactiflora cultivated in the presence of an NAD+-dependent HDAC inhibitor. Org. Lett.,15 (8), 2058-2061 (2013).

5.Asai T, Luo D, Yamashita K, Oshima Y. Structure and biomimetic synthesis of novel a-pyrone polyketides of an endophytic penicillium sp. Catharanthus roses.
Org. Lett., 15 (5), 1020-1023 (2013).

6.Asai T, Chung Y-M, Sakurai H, Ozeki T, Chang F-R, Wu Y-C, Yamashita K, Oshima Y. Highly oxidized ergosterols and isariotin analogs from an entomopathogenic fungus, Gibellula formosana, cultivated in the presence of epigenetic modifying agents. Tetrahedron, 68, 5817-5823 (2012).

7.Asai T, Luo D, Obara Y, Taniguchi T, Monde K, Yamashita K, Oshima Y. Dihydrobenzofurans as cannabinoid receptor ligands from Cordyceps annullata, an entomopathogenic fungus cultivated in the presence of an HDAC inhibitor.
Tetrahedron Lett.,53, 2239-2243 (2012).

8.Asai T, Chung Y-M, Sakurai H, Ozeki T, Chang F-R, Yamashita K, Oshima Y. Tenuipyrone, a novel skeletal polyketide from the entomopathogenic fungus, Isaria tenuipes, cultivated in the presence of epigenetic modifiers. Org. Lett., 14: 513-515 (2012).

9.Asai T, Yamamoto T, Chung Y-M, Chang F-R, Wu Y-C, Yamashita K, Oshima Y Aromatic polyketide glycosides from an entomopathogenic fungus, Cordyceps indigotica. Tetrahedron Lett., 53, 277-280 (2012).

10.Nakamura Y, Satoh F, Morimoto R, Kudo M, Takase K, Gometz-Sanchez C-E, Honma S, Okuyama M, Yamashita K, Rainey W-E, Sasano H, Ito S. 18-Oxocortisol measurement in adrenal vein sampling as a biomarker for subclassifying primary aldosteroism. J. Clin. Endocrinol. Metab., 96, E1272-1278 (2011).

11.Yamashita K, Masuda A, Hoshino Y, Komatsu S, Numazawa M. Assay of labile estrogen o-quinones, potent carcinogenic molecular species, by high performance liquid chromatography-electrospray ionization tandem mass spectrometry with phenazine derivatization. J. Steroid Biochem. Mol. Biol., 119, 141-148 (2010).

12.Honda A, Miyazaki T, Ikegami T, Iwamoto J, Yamashita K, Numazawa M, Matsuzaki M. Highly sensitive and specific analysis of sterol profiles in biological samples by HPLC-ESI-MS/MS. J.Steroid Biochem. Mol. Biol., 121, 556-564 (2010).

13.Takahashi M, Yamashita K, Numazawa M. Probing the binding pocket of the active site of aromatase with 2-phenylaliphatic androsta-1,4-diene-3,17-dione steroids.Steroids, 75, 330-337 (2010).

14.Yamashita K, Komatsu S, Yamazaki K, Numazawa N. Fusaric acid as a novel proton-affinitive derivatizing reagent for highly sensitive quantification of hydroxysteroids by LC-ESI-MS/MS. J.Am. Soc. Mass Spectrom., 21, 249-253 (2010).

15.Komatsu S, Yaguchi A, Yamashita K, Nagaoka M, Numazawa M. 6b,19-Bridged androstenedione analogs as aromatase inhibitors Steroids, 74, 884-889 (2009).

16.Takahashi M, Handa W, Umeta H, Ishikawa S, Yamashita K, Numazawa M. Aromatase inactivation by 2-substituted derivatives of the suicide substrate androsta-1,4-diene-3,17-dione. J. Steroid Biochem. Mol. Biol.,116, 191-199 (2009).

17.Yamashita K, Miyashiro Y, Maekubo H, Okuyama M, Honma S, Takahashi M, Numazawa M. Development of highly sensitive quantification method for testosterone and dihydrotestosterone in human serum and prostate tissue by liquid chromatography-electrospray ionization tandem mass spectrometry. Steroids, 74, 920-926 (2009).

18.Honda A, Yamashita K, Ikegami T, Hara T, Miyazaki T, Hirayama T, Numazawa M, Matsuzaki Y Highly sensitive quantification of serum malonate, a possible marker for de novo lipogenesis, by LC-ESI-MS/MS. J. Lipid Res.,50, 2124- 2130 (2009).

19.Yamashita K, Kawahata T, Takahashi M, Numazawa M. Microdetermination of catechol estrogens by LC-ESI-MS/MS combined with picolinyl derivatization.
J. Mass Spectrom. Soc., 57, 75-80 (2009).

20.Numazawa M, Yamashita K, Kimura N, Takahashi M Chemical aromatization of 19-hydroxyandrosta-1,4-diene-3,17-dione with acid or alkaline: Elimination of the 19-hydroxy methyl group as formaldehyde. Steroids, 74, 208-211 (2009).

21.Honda A, Yamashita K, Hara T, Ikegami T, Miyazaki M, Shirai M, Xu G, Numazawa M, Matsuzaki Y. Highly sensitive quantification of key regulatory oxysterols in biological samples by LC-ESI-MS/MS. J. Lipid Res., 50, 350-357 (2009)

22.Numazawa M, Komatsu S, Tominaga T, Yamashita K. Structure-activity relationships of estrogen derivatives as aromatase inhibitors. Effects of heterocyclic substituents. Chem. Pharm. Bull., 56, 1304-1309 (2008).

23.Numazawa M, Watari Y, Komatsu S, Yamashita K, Nagaoka M. Aromatization of androstenedione and 16a-hydroxyandrostenedione in human placental microsomes. Kinetic analysis of inhibition by the 19-oxygenated and 3-deoxy analogs. Steroids, 73, 1262-1269 (2008).

24.Honda A, Yamashita K, Miyazaki M, Shirai M, Ikegami T, Xu G, Numazawa M, Hara T, Matsuzaki Y. Highly sensitive analysis of sterol profiles in human serum by LC-ESI-MS/MS. J. Lipid. Res., 49, 2063-2073 (2008).

25.Yamashita K, Tadokoro T, Takahashi M, Numazawa M. Preparation and structural elucidation of the picolinyl ester of aldosterone for liquid chromatography-electrospray ionization tandem mass spectrometry. Chem.Pharm. Bull., 56: 873-877 (2008).

26.Numazawa M, Matsuzaki H, Nagaoka M, Yamashita K, Komatsu S, Osawa Y. Mechanistic aspects of rearrangement of 16a-Hydroxy-17-keto steroids to the 17b-hydroxy-16-keto isomers. Steroids, 73, 798-805 (2008).

27.Yamashita K, Nakagawa R, Okuyama M, Honma S, Takahashi M, Numazawa M. Simultaneous determination of tetrahydrocortisol, allo-tetrahydrocortisol and tetrahydrocortisone in human urine by LC-ESI-MS/MS. Steroids,73, 727-737 (2008).

28.Yamashita K, Okuyama M, Nakagawa R, Honma S, Satoh F, Morimoto R, Ito S, Takahashi M, Numazawa M. Development of sensitive derivatization method for aldosterone in liquid chromatography-electrospray ionization tandem mass spectrometry of corticosteroids. J. Chromatogr. A., 1200, 114-121 (2008).

29.Yamashita K, Takahashi M, Tsukamoto S, Numazawa M, Okuyama M, Honma S. Use of novel picolinoyl derivatization for simultaneous quantification of six corticosteroids by liquid chromatography-electrospray ionization tandem mass spectrometry. J. Chromatogr. A., 1173, 120-128 (2007).

30.Yamashita K, Okuyama M, Watanabe Y, Honma S, Kobayahsi S, Numazawa M. Highly sensitive determination of estrone and estradiol in human serum by liquid chromatography-electrospray ionization tandem mass spectrometry. Steroids, 72, 819-827 (2007).

31.Numazawa M, Takahashi M, Nagaoka M, Handa W, Yamashita K. Mass spectrometric analysis of oxygenations in aromatization of androst-4- ene-3,6,17-trione, a suicide substrate of aromatase, by placental microsomes. Isotope effect and stereochemistry. J. Steroid Biochem. Mol. Biol., 107, 220-227 (2007).

32.Yamashita K, Kobayashi S, Tsukamoto S, Numazawa M. Synthesis of pyridine-carboxylate derivatives of hydroxysteroids for liquid chromatography- electrospray ionization-mass spectrometry. Steroids,72, 50-59 (2007).

33.Honda A, Yamashita K, Numazawa M, Ikegami T, Doy M, Matsuzaki Y, Miyazaki M. Highly sensitive quantification of 7a-hydroxy-4-cholesten-3-one in human serum by LC-ESI-MS/MS. J. Lipid Res., 48, 458-464 (2007).

34.Niwa M, Watanabe N, Ochiai H, Yamashita K. Determination of testosterone concentration in rat plasma using liquid chromatography- atmospheric pressure chemical ionization tandem mass spectrometry combined with ethyloxime and acetyl derivatization. J. Chromatogr. B., 824, 258-266 (2005).

35.Kubata B K, Duszenko M, Kabatutu Z, Rawer M, Szallies A, Fujimori K, Inui T, Nozaki T, Yamashita K, Horii T, Urade Y, Hayaishi O. Identification of novel prostaglandin F2a synthease in Trypanosoma bruccei. J. Exp. Med., 192, 1327-1337 (2000).

外部競争的研究資金

(研究代表者 2000年以降)
1.科研費(基盤研究 C)(日本学術振興会):副腎皮質機能解析のためのtargeted steroidomics研究、2013‐2016年.

2.科研費(基盤研究 C)(日本学術振興会):エストロゲンオルトキノンの定量法の開発と乳がんの発がん機構解析への応用、2010‐2013年.

著書及び総説

(2000年以降)
1.山下幸和、よくわかる薬学機器分析(編集:藤岡稔大、二村典行、大庭義史、山下幸和)、“センサーとドライケミストリー” pp. 311-320、 “物理的分析法” pp. 322-336、廣川書店、2015年.

2.山下幸和、よくわかる薬学分析化学(編集:二村典行、大庭義史、山下幸和)、“化学平衡” pp. 41-58、 “定量(容量)分析”pp. 211-222、廣川書店、2014年.

3.Kouwa Yamashita, Mitsuteru Numazawa, Handbook on Mass Spectrometry: Instrumentation, Data and Analysis, and Application. (ed. byJ.K. Lang), “Proton-affinitive derivatization in LC-ESI-MS/MS analyses of hydroxysteroids” Chaper 18, 459-464, Nova Scientific Pub. Inc., USA(2009).

4.Kouwa Yamashita, Testosterone: Biochemistry, Therapeutic Uses and Physiological Effects. (ed. by K. Chichinadze)” Development of novel proton-affinitive derivatives for simultaneous analysis of testosterone and dihydrotestosterone in human serum and prostate tissue by LC-ESI-MS/MS”
Chapter VIII, 145-158, Nova Science Pub. Inc., USA (2012).

5.山下幸和、パートナー分析化学II改訂第2版 (編集:山口政俊、升島 努、能田 均)、“構造解析:概説”pp. 43-51、南江堂、2012年.

入試情報 ADMISSION