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Development of LC/MS methods for the...
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Yang, Shuming.
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Development of LC/MS methods for the PK and PD studies of drugs.
紀錄類型:
書目-電子資源 : Monograph/item
正題名/作者:
Development of LC/MS methods for the PK and PD studies of drugs./
作者:
Yang, Shuming.
面頁冊數:
139 p.
附註:
Source: Dissertation Abstracts International, Volume: 64-12, Section: B, page: 6067.
Contained By:
Dissertation Abstracts International64-12B.
標題:
Chemistry, Analytical. -
電子資源:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3115019
Development of LC/MS methods for the PK and PD studies of drugs.
Yang, Shuming.
Development of LC/MS methods for the PK and PD studies of drugs.
- 139 p.
Source: Dissertation Abstracts International, Volume: 64-12, Section: B, page: 6067.
Thesis (Ph.D.)--Cleveland State University, 2003.
LC/ESI-MS is the most powerful analytical tool for method development of small molecular drugs in biological matrix, which usually requires three steps: sample preparation, separation, and detection. ESI-MS-MS has the ability to detect one single targeted analyte from complicated mixture. This dissertation explored the feasibility of direct combination of on-line SPE with ESI-MS-MS in rapid method development of small molecules in plasma or serum, which can be used as a generic method. This dissertation also investigated the LC factors affecting detection sensitivity in reverse-phase LC/ESI-MS method development, and the linking of weak anion exchange LC to ESI-MS.Subjects--Topical Terms:
586156
Chemistry, Analytical.
Development of LC/MS methods for the PK and PD studies of drugs.
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LC/ESI-MS is the most powerful analytical tool for method development of small molecular drugs in biological matrix, which usually requires three steps: sample preparation, separation, and detection. ESI-MS-MS has the ability to detect one single targeted analyte from complicated mixture. This dissertation explored the feasibility of direct combination of on-line SPE with ESI-MS-MS in rapid method development of small molecules in plasma or serum, which can be used as a generic method. This dissertation also investigated the LC factors affecting detection sensitivity in reverse-phase LC/ESI-MS method development, and the linking of weak anion exchange LC to ESI-MS.
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The feasibility of combining on-line SPE and ESI-MS-MS was demonstrated by the method development, validation and application for both melatonin in human serum and methoxyamine (CH3ONH2) in human or mouse plasma. Methoxyamine was derivatized directly in plasma by 4-(N, N-diethylamino)benzaldehyde. For both melatonin and methoxyamine, the diluted serum or plasma was injected into the on-line extraction column. After the removal of proteins, the retained analyes were eluted and directed into ESI-MS-MS. For both melatonin and methoxyamine, this method had excellent sensitivity and very short analysis time, and showed no any interference. The method has been successfully applied for the pharmacokinetic (PK) study of methoxyamine in mice.
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Genistein was found to have identical ionization efficiency with daidzein in negative ESI-MS-MS. The LC factors affecting ESI-MS-MS detection, such as mobile phase composition, pH, and salt concentration, was demonstrated by developing reverse-phase LC/negative ESI-MS-MS method for genistein and daidzein in human plasma.
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Ion exchange LC is not compatible with ESI-MS detection when inorganic salt is used. But the linking of weak anion exchange LC to ESI-MS-MS was proved to be feasible when volatile organic salt was used. This combination was confirmed by the method development for the quantitative determination of sialic acid analogs, which used amino column with negative ESI-MS-MS detection.
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