Quantification of belatacept by liquid chromatography-tandem mass spectrometry in human plasma : Application to a pharmacokinetic study in renal transplant recipients
Copyright © 2022 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved..
Therapeutic drug monitoring is the cornerstone of immunosuppressive treatment in transplantation. The immunosuppressive drugs used in kidney transplant patients are mostly comprised of biologics, including therapeutic monoclonal antibodies (mAbs) and fusion proteins. Therefore, a specific and sensitive analytical technique that can universally quantify mAbs, as well as fusion proteins, is essential for clinical pharmacokinetics studies. In this short communication, we describe the validation of a liquid chromatography tandem mass-spectrometry (LC-MS/MS) method for quantification of the fusion protein belatacept in the plasma of kidney-transplant patients. Sample preparation was based on our previously published and implementable electrospray ionization LC-MS/MS method that allows the simultaneous quantification of seven mAbs. Immunocapture was made possible by the Fc domain of belatacept and identification/quantification by the choice of MRM transitions of peptides. The temporal evolution of the belatacept concentration after intravenous infusion and inter-individual variability of trough concentrations were assessed in 17 human plasma samples. The belatacept calibration curves were linear from 1 to 200 mg.L-1 and within-day and between-day accuracy and precision fulfilled Food and Drug Administration validation criteria. Residual belatacept concentrations (n = 8) ranged from 5.1 to 15.0 mg.L-1, with a median of 8.9 mg.L-1 and an inter-individual CV of 33.0%. Our generic LC-MS/MS method allows the quantification of fusion proteins, such as belatacept, and could be used for therapeutic drug monitoring. This method provides a useful tool to study the intra-patient variability of belatacept and the association between belatacept exposure and its therapeutic effects.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:113 |
|---|---|
| Enthalten in: |
Clinical biochemistry - 113(2023) vom: 15. März, Seite 17-20 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Truffot, Aurélie [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 14.02.2023 Date Revised 14.02.2023 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.clinbiochem.2022.12.014 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM350978948 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM350978948 | ||
| 003 | DE-627 | ||
| 005 | 20231226050225.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.clinbiochem.2022.12.014 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1169.xml |
| 035 | |a (DE-627)NLM350978948 | ||
| 035 | |a (NLM)36586569 | ||
| 035 | |a (PII)S0009-9120(22)00296-X | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Truffot, Aurélie |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Quantification of belatacept by liquid chromatography-tandem mass spectrometry in human plasma |b Application to a pharmacokinetic study in renal transplant recipients |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 14.02.2023 | ||
| 500 | |a Date Revised 14.02.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2022 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a Therapeutic drug monitoring is the cornerstone of immunosuppressive treatment in transplantation. The immunosuppressive drugs used in kidney transplant patients are mostly comprised of biologics, including therapeutic monoclonal antibodies (mAbs) and fusion proteins. Therefore, a specific and sensitive analytical technique that can universally quantify mAbs, as well as fusion proteins, is essential for clinical pharmacokinetics studies. In this short communication, we describe the validation of a liquid chromatography tandem mass-spectrometry (LC-MS/MS) method for quantification of the fusion protein belatacept in the plasma of kidney-transplant patients. Sample preparation was based on our previously published and implementable electrospray ionization LC-MS/MS method that allows the simultaneous quantification of seven mAbs. Immunocapture was made possible by the Fc domain of belatacept and identification/quantification by the choice of MRM transitions of peptides. The temporal evolution of the belatacept concentration after intravenous infusion and inter-individual variability of trough concentrations were assessed in 17 human plasma samples. The belatacept calibration curves were linear from 1 to 200 mg.L-1 and within-day and between-day accuracy and precision fulfilled Food and Drug Administration validation criteria. Residual belatacept concentrations (n = 8) ranged from 5.1 to 15.0 mg.L-1, with a median of 8.9 mg.L-1 and an inter-individual CV of 33.0%. Our generic LC-MS/MS method allows the quantification of fusion proteins, such as belatacept, and could be used for therapeutic drug monitoring. This method provides a useful tool to study the intra-patient variability of belatacept and the association between belatacept exposure and its therapeutic effects | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Belatacept | |
| 650 | 4 | |a Fusion protein | |
| 650 | 4 | |a Kidney transplant | |
| 650 | 4 | |a Liquid-chromatography tandem mass spectrometry | |
| 650 | 4 | |a Therapeutic drug monitoring | |
| 650 | 7 | |a Abatacept |2 NLM | |
| 650 | 7 | |a 7D0YB67S97 |2 NLM | |
| 650 | 7 | |a Immunosuppressive Agents |2 NLM | |
| 650 | 7 | |a Antibodies, Monoclonal |2 NLM | |
| 700 | 1 | |a Jourdil, Jean-François |e verfasserin |4 aut | |
| 700 | 1 | |a Veyret-Gautier, Elodie |e verfasserin |4 aut | |
| 700 | 1 | |a Noble, Johan |e verfasserin |4 aut | |
| 700 | 1 | |a Jouve, Thomas |e verfasserin |4 aut | |
| 700 | 1 | |a Malvezzi, Paolo |e verfasserin |4 aut | |
| 700 | 1 | |a Rostaing, Lionel |e verfasserin |4 aut | |
| 700 | 1 | |a Stanke-Labesque, Françoise |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Clinical biochemistry |d 1970 |g 113(2023) vom: 15. März, Seite 17-20 |w (DE-627)NLM000001988 |x 1873-2933 |7 nnns |
| 773 | 1 | 8 | |g volume:113 |g year:2023 |g day:15 |g month:03 |g pages:17-20 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.clinbiochem.2022.12.014 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 113 |j 2023 |b 15 |c 03 |h 17-20 | ||