Mechanistic Study on the Cortisol Metabolism and Secretion in the Endocrinological Disorders

内分泌疾病中皮质醇代谢与分泌的机制研究

• 批准号: 04807168
• 负责人: KASUYA Yasuji
• 金额: $ 1.28万
• 依托单位: Tokyo College of Pharmacy
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04807168/
• 关键词: Stable isotopes; Deuterium labeling; Cortisol; Cortisone; Prednisolone; Prednisone; GC-MS; Pharmacokinetics; GC‐MS法; ステロイドホルモン分泌異常機構

Stable isotope methodology coupled with GC-MS is widely accepted as the most accurate and specific method for estimation of the small amounts of endogenous and synthetic steroids in biological fluids. In this technique, the use of stable isotopically labeled analogues as internal standards offers major advantages of compasating for losses of material at all stages of sample handling, which may not be the case with internal standards possessing a different structure from the compound under investigation.The use of isotopically labeled compounds as tracers has also enjoyed broad application in metabolic studies. One of the major advantages of this technique is that an endogenous compound and its stable isotopically labeled analogue exogenously administered can be differentiated easily by employing mass spectrometry.We have developed a capillary GC-MS method for the simultaneous assay of cortisol, cortisone, prednisolone, and prednisone in human plasma using their respective deuteratede analogs synthesized in our laboratory as internal standards. The method has been applied for the phamacokinetic study of prednisolone in a pediatric patient with nephrosis.

稳定同位素方法结合GC-MS被广泛认为是估计生物体液中少量内源性和合成类固醇的最准确和特异性的方法。在该技术中，使用稳定的同位素标记的类似物作为内标物提供了在样品处理的所有阶段比较材料损失的主要优点，这可能不是具有与所研究的化合物不同的结构的内标物的情况。该技术的主要优点之一是，内源性化合物和其稳定的同位素标记的类似物外源管理可以很容易地区分通过采用massspectrometry.We开发了毛细管气相色谱-质谱法同时测定皮质醇，可的松，泼尼松龙，泼尼松在人血浆中使用各自的氘代类似物在我们的实验室合成的内标。该方法已应用于泼尼松龙在小儿肾病患者的药代动力学研究。

项目成果

H. Shibasaki, T. Furuta, and Y. Kasuya: "Stable isotope diluton mass spectrometry for the simultaneous determidnation of cortisol, cortisone, prednisolone and prednisone in plasma" Journal of Chromatography. 579. 193-202 (1992)

H. Shibasaki、T. Furuta 和 Y. Kasuya：“稳定同位素稀释质谱法同时测定血浆中的皮质醇、可的松、泼尼松龙和泼尼松”《色谱杂志》。

H. Shibasaki, T. Furuta, and Y. Kasuya: "Preparation of multiply deuterium‐labeled cortisol" Steroids. 57. 13-17 (1992)

H. Shibasaki、T. Furuta 和 Y. Kasuya：“多重氘标记皮质醇的制备”类固醇。57. 13-17 (1992)

H.Shibasaki,T.Furuta and Y.Kasuya: "Stereochemical Aspects in the Enantioselective Synthesis of Cortisone by the Indan Synthon Method" Steroids. 57. 325-327 (1992)

H.Shibasaki、T.Furuta 和 Y.Kasuya：“通过茚满合成法对映选择性合成可的松的立体化学方面”类固醇。

H.Shibasaki,T.Furuta and Y.Kasuya: "Simultaneous Determination of Cortisol,Cortisone,Prednisolone,and Prednisone byThermospray LC-MS" J.Chromatography. (発表予定).

H.Shibasaki、T.Furuta 和 Y.Kasuya：“通过热喷雾 LC-MS 同时测定皮质醇、可的松、泼尼松龙和泼尼松”J. 色谱法。

Hiromi Shibasaki: "Synthesis of Multiply Deuterium-Labelled Prednisone and Prednisolone" J.Labelled Compd.Radiopharm.29. 1033-1040 (1991)

Hiromi Shibasaki：“多重氘标记泼尼松和泼尼松龙的合成”J.Labeled Compd.Radiopharm.29。