Investigating surrogate cerebrospinal fluid matrix compositions for use in quantitative LC-MS analysis of therapeutic antibodies in the cerebrospinal fluid
| Autor: | Kasper D. Rand, Anne-Marie Jacobsen, Line Olsen, Tam T. T. N. Nguyen, Jens Rose Fogh |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Serial dilution
medicine.drug_class Monoclonal antibody 01 natural sciences Biochemistry Antibodies Analytical Chemistry Matrix (chemical analysis) 03 medical and health sciences Cerebrospinal fluid Dogs Liquid chromatography–mass spectrometry Tandem Mass Spectrometry medicine Animals Humans Sample preparation Amino Acid Sequence Bovine serum albumin 030304 developmental biology 0303 health sciences Chromatography Cerebrospinal fluid (CSF) biology Surrogate matrix Chemistry 010401 analytical chemistry Haplorhini Reference Standards Monoclonal antibodies (mAbs) 0104 chemical sciences Rats Bioanalysis Calibration biology.protein Liquid chromatography-mass spectrometry (LC-MS) Quantitative analysis (chemistry) Research Paper Chromatography Liquid |
| Zdroj: | Analytical and Bioanalytical Chemistry Fogh, J R, Jacobsen, A-M, Nguyen, T T T N, Rand, K D & Olsen, L R 2020, ' Investigating surrogate cerebrospinal fluid matrix compositions for use in quantitative LC-MS analysis of therapeutic antibodies in the cerebrospinal fluid ', Analytical and Bioanalytical Chemistry, vol. 412, pp. 1653-1661 . https://doi.org/10.1007/s00216-020-02403-3 |
| ISSN: | 1618-2650 1618-2642 |
| DOI: | 10.1007/s00216-020-02403-3 |
| Popis: | As quantitative analysis of biotherapeutics in cerebrospinal fluid (CSF) with LC-MS becomes increasingly widespread, there is a need for method developments towards higher sensitivity. By using artificial CSF (aCSF) in the development phase, the consumption of costly and sparsely available CSF can be limited. The aCSF compositions tested here were made from various dilutions of bovine serum albumin (BSA) or rat plasma to mimic the total protein concentration found in CSF. Focusing on monoclonal antibodies, the aCSF was spiked with human immunoglobulin (hIgG) and prepared with the bottom-up analysis technique using LC-MS. Assuming that the composition of the aCSF would affect the digest, the response from aCSF matrices was compared with CSF from rat, monkey, and dog in terms of estimated sample concentration and matrix effects. The samples were spiked with hIgG in the range of 10 to 1000 ng/mL and volumes of 10 μL were transferred to sample preparation. The results indicate that BSA dilutions from 300 to 2000 μg/mL and rat plasma dilutions of 0.5–2% provide the most accurate concentration estimates when compared with rat CSF. 1000 μg/mL BSA did not produce significantly different concentration estimates for 500 ng/mL samples when compared with CSF from rat, monkey, and dog, and can therefore be used as aCSF for several different species. Electronic supplementary material The online version of this article (10.1007/s00216-020-02403-3) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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