Rapid Screening of Drug-Protein Binding Using High-Performance Affinity Chromatography with Columns Containing Immobilized Human Serum Albumin
For drug candidates, a plasma protein binding (PPB) more than 90% is more meaningful and deserves further investigation in development. In the study, a high-performance liquid chromatography method employing column containing immobilized human serum albumin (HSA) to screen in vitro PPB of leading co...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2013-01-01
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| Series: | Journal of Analytical Methods in Chemistry |
| Online Access: | http://dx.doi.org/10.1155/2013/439039 |
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| author | Ying-Fei Li Xiao-Qiong Zhang Wei-Yu Hu Zheng Li Ping-Xia Liu Zhen-Qing Zhang |
| author_facet | Ying-Fei Li Xiao-Qiong Zhang Wei-Yu Hu Zheng Li Ping-Xia Liu Zhen-Qing Zhang |
| author_sort | Ying-Fei Li |
| collection | DOAJ |
| description | For drug candidates, a plasma protein binding (PPB) more than 90% is more meaningful and deserves further investigation in development. In the study, a high-performance liquid chromatography method employing column containing immobilized human serum albumin (HSA) to screen in vitro PPB of leading compounds was established and successfully applied to tested compounds. Good correlation (a coefficient correlation of 0.96) was attained between the reciprocal values (X) of experimentally obtained retention time of reference compounds eluted through HSA column and the reported PPB values (Y) with a correlation equation of Y =92.03−97.01X. The method was successfully applied to six test compounds, and the result was confirmed by the conventional ultrafiltration technique, and both yielded equal results. However, due to the particular protein immobilized to column, the method cannot be applied for all compounds and should be exploited judiciously based on the value of the logarithmic measure of the acid dissociation constant (pKa) as per the requirement. If α1-acid glycoprotein and other plasma proteins could be immobilized like HSA with their actual ratio in plasma to column simultaneously, the result attained using immobilized column may be more accurate, and the method could be applied to more compounds without pKa limitation. |
| format | Article |
| id | doaj-art-b147d4e4470c4dbcbb3ee8300e4bf2d8 |
| institution | OA Journals |
| issn | 2090-8865 2090-8873 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Analytical Methods in Chemistry |
| spelling | doaj-art-b147d4e4470c4dbcbb3ee8300e4bf2d82025-08-20T02:23:35ZengWileyJournal of Analytical Methods in Chemistry2090-88652090-88732013-01-01201310.1155/2013/439039439039Rapid Screening of Drug-Protein Binding Using High-Performance Affinity Chromatography with Columns Containing Immobilized Human Serum AlbuminYing-Fei Li0Xiao-Qiong Zhang1Wei-Yu Hu2Zheng Li3Ping-Xia Liu4Zhen-Qing Zhang5Beijing Institute of Pharmacology and Toxicology, Beijing 100850, ChinaBeijing Institute of Pharmacology and Toxicology, Beijing 100850, ChinaHepatobiliary Surgery Department, The Affiliated Hospital of Medical College, Qingdao University, Qingdao 266003, ChinaBeijing Institute of Pharmacology and Toxicology, Beijing 100850, ChinaBeijing Institute of Pharmacology and Toxicology, Beijing 100850, ChinaBeijing Institute of Pharmacology and Toxicology, Beijing 100850, ChinaFor drug candidates, a plasma protein binding (PPB) more than 90% is more meaningful and deserves further investigation in development. In the study, a high-performance liquid chromatography method employing column containing immobilized human serum albumin (HSA) to screen in vitro PPB of leading compounds was established and successfully applied to tested compounds. Good correlation (a coefficient correlation of 0.96) was attained between the reciprocal values (X) of experimentally obtained retention time of reference compounds eluted through HSA column and the reported PPB values (Y) with a correlation equation of Y =92.03−97.01X. The method was successfully applied to six test compounds, and the result was confirmed by the conventional ultrafiltration technique, and both yielded equal results. However, due to the particular protein immobilized to column, the method cannot be applied for all compounds and should be exploited judiciously based on the value of the logarithmic measure of the acid dissociation constant (pKa) as per the requirement. If α1-acid glycoprotein and other plasma proteins could be immobilized like HSA with their actual ratio in plasma to column simultaneously, the result attained using immobilized column may be more accurate, and the method could be applied to more compounds without pKa limitation.http://dx.doi.org/10.1155/2013/439039 |
| spellingShingle | Ying-Fei Li Xiao-Qiong Zhang Wei-Yu Hu Zheng Li Ping-Xia Liu Zhen-Qing Zhang Rapid Screening of Drug-Protein Binding Using High-Performance Affinity Chromatography with Columns Containing Immobilized Human Serum Albumin Journal of Analytical Methods in Chemistry |
| title | Rapid Screening of Drug-Protein Binding Using High-Performance Affinity Chromatography with Columns Containing Immobilized Human Serum Albumin |
| title_full | Rapid Screening of Drug-Protein Binding Using High-Performance Affinity Chromatography with Columns Containing Immobilized Human Serum Albumin |
| title_fullStr | Rapid Screening of Drug-Protein Binding Using High-Performance Affinity Chromatography with Columns Containing Immobilized Human Serum Albumin |
| title_full_unstemmed | Rapid Screening of Drug-Protein Binding Using High-Performance Affinity Chromatography with Columns Containing Immobilized Human Serum Albumin |
| title_short | Rapid Screening of Drug-Protein Binding Using High-Performance Affinity Chromatography with Columns Containing Immobilized Human Serum Albumin |
| title_sort | rapid screening of drug protein binding using high performance affinity chromatography with columns containing immobilized human serum albumin |
| url | http://dx.doi.org/10.1155/2013/439039 |
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