Development of Quantitative LC-MS/MS Methods for the Pharmacological Studies of Anti-Cancer Drugs
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Cleveland State University / OhioLINK
2011
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| Online Access: | http://rave.ohiolink.edu/etdc/view?acc_num=csu1299117212 |
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ndltd-OhioLink-oai-etd.ohiolink.edu-csu12991172122021-08-03T05:35:19Z Development of Quantitative LC-MS/MS Methods for the Pharmacological Studies of Anti-Cancer Drugs Li, Lan LC-MS/MS 6BT DNA MX-AP F-ARA-A F-Ade In the development of anti-cancer drugs, it is essential to study the pharmacological profiles of the drugs. Among the analytical tools utilized in the pharmacological studies, LC-MS/MS has gained increased popularity due to its unequivocal sensitivity and specificity, as well as the ability of handling a wide variety of compounds with relatively simple sample preparation procedures. In this work, a brief review on the method rational, instrumentations, analytical method validation, and work flow of the method development was included. The processes of LC-MS/MS method development for the pharmacological studies of three anti-cancer drugs (i.e., methoxyamine, fludarabine, and 6-benzylthioinosine) were illustrated. To be more specific, a tetra-enzyme cocktail utilized for DNA adducts release was introduced. LC-MS/MS methods for the analysis of methoxyamine modified DNA abasic sites and fludarabine incorporated in DNA were developed toward the DNA adducts released from DNA with the enzyme cocktail. The methods were applied to the drug effect and drug mechanism studies. Another two LC-MS/MS method was developed for the quantification of 2-fluoroadenine released from the fludarabine incorporated DNA and free 6-benzylthioinosine drug molecule in mouse and human plasma. The first method helped to provide direct evidence to a newly proposed drug resistance mechanism toward fludarabine through DNA base excision repair; while the second method realized the pharmacokinetic studies of the drug. The results in this work not only demonstrated the capability of LC-MS/MS in solving sophisticated pharmacological puzzles, but will provide useful information guiding the preclinical studies and clinical therapy development of the anti-cancer drugs listed above. 2011-03-03 English text Cleveland State University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=csu1299117212 http://rave.ohiolink.edu/etdc/view?acc_num=csu1299117212 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws. |
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NDLTD |
| language |
English |
| sources |
NDLTD |
| topic |
LC-MS/MS 6BT DNA MX-AP F-ARA-A F-Ade |
| spellingShingle |
LC-MS/MS 6BT DNA MX-AP F-ARA-A F-Ade Li, Lan Development of Quantitative LC-MS/MS Methods for the Pharmacological Studies of Anti-Cancer Drugs |
| author |
Li, Lan |
| author_facet |
Li, Lan |
| author_sort |
Li, Lan |
| title |
Development of Quantitative LC-MS/MS Methods for the Pharmacological Studies of Anti-Cancer Drugs |
| title_short |
Development of Quantitative LC-MS/MS Methods for the Pharmacological Studies of Anti-Cancer Drugs |
| title_full |
Development of Quantitative LC-MS/MS Methods for the Pharmacological Studies of Anti-Cancer Drugs |
| title_fullStr |
Development of Quantitative LC-MS/MS Methods for the Pharmacological Studies of Anti-Cancer Drugs |
| title_full_unstemmed |
Development of Quantitative LC-MS/MS Methods for the Pharmacological Studies of Anti-Cancer Drugs |
| title_sort |
development of quantitative lc-ms/ms methods for the pharmacological studies of anti-cancer drugs |
| publisher |
Cleveland State University / OhioLINK |
| publishDate |
2011 |
| url |
http://rave.ohiolink.edu/etdc/view?acc_num=csu1299117212 |
| work_keys_str_mv |
AT lilan developmentofquantitativelcmsmsmethodsforthepharmacologicalstudiesofanticancerdrugs |
| _version_ |
1719422121087598592 |