A Comprehensive Immunocapture-LC-MS/MS Bioanalytical Approach in Support of a Biotherapeutic Ocular PK Study
BI-X, a therapeutic protein under development for the treatment of human ocular disease via intravitreal administration, binds to its therapeutic targets and endogenous albumin in the vitreous humor. A monkey ocular pharmacokinetic (PK) study following BI-X administration was conducted to measure dr...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-01-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/17/2/193 |
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| author | Lin-Zhi Chen David Roos Elsy Philip Emily G. Werth Stephanie Kostuk Hongbin Yu Holger Fuchs |
| author_facet | Lin-Zhi Chen David Roos Elsy Philip Emily G. Werth Stephanie Kostuk Hongbin Yu Holger Fuchs |
| author_sort | Lin-Zhi Chen |
| collection | DOAJ |
| description | BI-X, a therapeutic protein under development for the treatment of human ocular disease via intravitreal administration, binds to its therapeutic targets and endogenous albumin in the vitreous humor. A monkey ocular pharmacokinetic (PK) study following BI-X administration was conducted to measure drug and albumin levels in plasma, the vitreous humor, the aqueous humor, and retina tissue at various timepoints post-dose. A comprehensive bioanalytical approach was implemented in support of this study. Five immunocapture-LC-MS/MS assays were developed and qualified for quantitating BI-X in different matrices, while ELISA was used for albumin measurement. Immunocapture at the protein or peptide level was evaluated to achieve adequate assay sensitivity. Drug and albumin assays were applied for the analysis of the monkey study samples. |
| first_indexed | 2024-03-07T22:17:59Z |
| format | Article |
| id | doaj.art-7a011e49b1bc40a7b8551599e66b1f2b |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-07T22:17:59Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-7a011e49b1bc40a7b8551599e66b1f2b2024-02-23T15:30:38ZengMDPI AGPharmaceuticals1424-82472024-01-0117219310.3390/ph17020193A Comprehensive Immunocapture-LC-MS/MS Bioanalytical Approach in Support of a Biotherapeutic Ocular PK StudyLin-Zhi Chen0David Roos1Elsy Philip2Emily G. Werth3Stephanie Kostuk4Hongbin Yu5Holger Fuchs6Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT 06877, USABoehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT 06877, USABoehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT 06877, USABoehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT 06877, USABoehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT 06877, USABoehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT 06877, USABoehringer Ingelheim Pharma GmbH & Co. KG, 88397 Biberach an der Riss, GermanyBI-X, a therapeutic protein under development for the treatment of human ocular disease via intravitreal administration, binds to its therapeutic targets and endogenous albumin in the vitreous humor. A monkey ocular pharmacokinetic (PK) study following BI-X administration was conducted to measure drug and albumin levels in plasma, the vitreous humor, the aqueous humor, and retina tissue at various timepoints post-dose. A comprehensive bioanalytical approach was implemented in support of this study. Five immunocapture-LC-MS/MS assays were developed and qualified for quantitating BI-X in different matrices, while ELISA was used for albumin measurement. Immunocapture at the protein or peptide level was evaluated to achieve adequate assay sensitivity. Drug and albumin assays were applied for the analysis of the monkey study samples.https://www.mdpi.com/1424-8247/17/2/193anti-drug antibodyanti-peptide antibodyimmunocapture-LC/MSsurrogate peptidealbuminhalf-life extension |
| spellingShingle | Lin-Zhi Chen David Roos Elsy Philip Emily G. Werth Stephanie Kostuk Hongbin Yu Holger Fuchs A Comprehensive Immunocapture-LC-MS/MS Bioanalytical Approach in Support of a Biotherapeutic Ocular PK Study Pharmaceuticals anti-drug antibody anti-peptide antibody immunocapture-LC/MS surrogate peptide albumin half-life extension |
| title | A Comprehensive Immunocapture-LC-MS/MS Bioanalytical Approach in Support of a Biotherapeutic Ocular PK Study |
| title_full | A Comprehensive Immunocapture-LC-MS/MS Bioanalytical Approach in Support of a Biotherapeutic Ocular PK Study |
| title_fullStr | A Comprehensive Immunocapture-LC-MS/MS Bioanalytical Approach in Support of a Biotherapeutic Ocular PK Study |
| title_full_unstemmed | A Comprehensive Immunocapture-LC-MS/MS Bioanalytical Approach in Support of a Biotherapeutic Ocular PK Study |
| title_short | A Comprehensive Immunocapture-LC-MS/MS Bioanalytical Approach in Support of a Biotherapeutic Ocular PK Study |
| title_sort | comprehensive immunocapture lc ms ms bioanalytical approach in support of a biotherapeutic ocular pk study |
| topic | anti-drug antibody anti-peptide antibody immunocapture-LC/MS surrogate peptide albumin half-life extension |
| url | https://www.mdpi.com/1424-8247/17/2/193 |
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