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Ocrelizumab quantitation by liquid chromatography-tandem mass spectrometry
INTRODUCTION: Ocrelizumab is a monoclonal anti-CD20 antibody approved for the treatment of multiple sclerosis (MS). The clinical value of therapeutic drug monitoring (TDM) for this antibody in treatment of MS is unknown, and an adequately specific and precise quantitation method for ocrelizumab in p...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9334332/ https://www.ncbi.nlm.nih.gov/pubmed/35910410 http://dx.doi.org/10.1016/j.jmsacl.2022.07.004 |
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author | Hallin, Erik I. Trætteberg Serkland, Trond Myhr, Kjell-Morten Grytten Torkildsen, Øivind Skrede, Silje |
author_facet | Hallin, Erik I. Trætteberg Serkland, Trond Myhr, Kjell-Morten Grytten Torkildsen, Øivind Skrede, Silje |
author_sort | Hallin, Erik I. |
collection | PubMed |
description | INTRODUCTION: Ocrelizumab is a monoclonal anti-CD20 antibody approved for the treatment of multiple sclerosis (MS). The clinical value of therapeutic drug monitoring (TDM) for this antibody in treatment of MS is unknown, and an adequately specific and precise quantitation method for ocrelizumab in patient serum could facilitate investigation. Liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based quantitation methods have been shown to have higher analytic specificity and precision than enzyme-linked immunosorbent assays. OBJECTIVES: To establish and validate an LC-MS/MS-based quantitation method for ocrelizumab. METHODS: We present an LC-MS/MS-based quantitation method using immunocapture purification followed by trypsinization and analysis by a triple quadrupole mass analyzer obtaining results within the same day. RESULTS: We found that the ocrelizumab peptide GLEWVGAIYPGNGDTSYNQK (Q1/Q3 Quantifier ion: 723.68(3+)/590.77 y11(2+) Qualifier ion: 723.68(3+)/672.30 y12(2+)) can be used for quantitation and thereby developed a method for quantifying ocrelizumab in human serum with a quantitation range of 1.56 to 200 µg/mL. The method was validated in accordance with EMA requirements in terms of selectivity, carry-over, lower limit of quantitation, calibration curve, accuracy, precision and matrix effect. Ocrelizumab serum concentrations were measured in three MS patients treated with ocrelizumab, immediately before and after ocrelizumab infusion, with additional sampling after 2, 4, 8 and 12 weeks. Measured serum concentrations of ocrelizumab showed expected values for both Cmax and drug half-life over the sampled time period. CONCLUSION: We have established a reliable quantitation method for serum ocrelizumab that can be applied in clinical studies, facilitating the evaluation of ocrelizumab TDM in MS. |
format | Online Article Text |
id | pubmed-9334332 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-93343322022-07-30 Ocrelizumab quantitation by liquid chromatography-tandem mass spectrometry Hallin, Erik I. Trætteberg Serkland, Trond Myhr, Kjell-Morten Grytten Torkildsen, Øivind Skrede, Silje J Mass Spectrom Adv Clin Lab Regular Article INTRODUCTION: Ocrelizumab is a monoclonal anti-CD20 antibody approved for the treatment of multiple sclerosis (MS). The clinical value of therapeutic drug monitoring (TDM) for this antibody in treatment of MS is unknown, and an adequately specific and precise quantitation method for ocrelizumab in patient serum could facilitate investigation. Liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based quantitation methods have been shown to have higher analytic specificity and precision than enzyme-linked immunosorbent assays. OBJECTIVES: To establish and validate an LC-MS/MS-based quantitation method for ocrelizumab. METHODS: We present an LC-MS/MS-based quantitation method using immunocapture purification followed by trypsinization and analysis by a triple quadrupole mass analyzer obtaining results within the same day. RESULTS: We found that the ocrelizumab peptide GLEWVGAIYPGNGDTSYNQK (Q1/Q3 Quantifier ion: 723.68(3+)/590.77 y11(2+) Qualifier ion: 723.68(3+)/672.30 y12(2+)) can be used for quantitation and thereby developed a method for quantifying ocrelizumab in human serum with a quantitation range of 1.56 to 200 µg/mL. The method was validated in accordance with EMA requirements in terms of selectivity, carry-over, lower limit of quantitation, calibration curve, accuracy, precision and matrix effect. Ocrelizumab serum concentrations were measured in three MS patients treated with ocrelizumab, immediately before and after ocrelizumab infusion, with additional sampling after 2, 4, 8 and 12 weeks. Measured serum concentrations of ocrelizumab showed expected values for both Cmax and drug half-life over the sampled time period. CONCLUSION: We have established a reliable quantitation method for serum ocrelizumab that can be applied in clinical studies, facilitating the evaluation of ocrelizumab TDM in MS. Elsevier 2022-07-22 /pmc/articles/PMC9334332/ /pubmed/35910410 http://dx.doi.org/10.1016/j.jmsacl.2022.07.004 Text en © 2022 THE AUTHORS https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Regular Article Hallin, Erik I. Trætteberg Serkland, Trond Myhr, Kjell-Morten Grytten Torkildsen, Øivind Skrede, Silje Ocrelizumab quantitation by liquid chromatography-tandem mass spectrometry |
title | Ocrelizumab quantitation by liquid chromatography-tandem mass spectrometry |
title_full | Ocrelizumab quantitation by liquid chromatography-tandem mass spectrometry |
title_fullStr | Ocrelizumab quantitation by liquid chromatography-tandem mass spectrometry |
title_full_unstemmed | Ocrelizumab quantitation by liquid chromatography-tandem mass spectrometry |
title_short | Ocrelizumab quantitation by liquid chromatography-tandem mass spectrometry |
title_sort | ocrelizumab quantitation by liquid chromatography-tandem mass spectrometry |
topic | Regular Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9334332/ https://www.ncbi.nlm.nih.gov/pubmed/35910410 http://dx.doi.org/10.1016/j.jmsacl.2022.07.004 |
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