Cross-Validation of a Multiplex LC-MS/MS Method for Assaying mAbs Plasma Levels in Patients with Cancer: A GPCO-UNICANCER Study.
LC–MS/MS
biologics
cross-validation
immunotherapy
therapeutic drug monitoring
Journal
Pharmaceuticals (Basel, Switzerland)
ISSN: 1424-8247
Titre abrégé: Pharmaceuticals (Basel)
Pays: Switzerland
ID NLM: 101238453
Informations de publication
Date de publication:
12 Aug 2021
12 Aug 2021
Historique:
received:
09
06
2021
revised:
28
07
2021
accepted:
02
08
2021
entrez:
28
8
2021
pubmed:
29
8
2021
medline:
29
8
2021
Statut:
epublish
Résumé
Different liquid chromatography tandem mass spectrometry (LC-MS/MS) methods have been published for quantification of monoclonal antibodies (mAbs) in plasma but thus far none allowed the simultaneous quantification of several mAbs, including immune checkpoint inhibitors. We developed and validated an original multiplex LC-MS/MS method using a ready-to-use kit to simultaneously assay 7 mAbs (i.e., bevacizumab, cetuximab, ipilimumab, nivolumab, pembrolizumab, rituximab and trastuzumab) in plasma. This method was next cross-validated with respective reference methods (ELISA or LC-MS/MS). The mAbXmise kit was used for mAb extraction and full-length stable-isotope-labeled antibodies as internal standards. The LC-MS/MS method was fully validated following current EMA guidelines. Each cross validation between reference methods and ours included 16-28 plasma samples from cancer patients. The method was linear from 2 to 100 µg/mL for all mAbs. Inter- and intra-assay precision was <14.6% and accuracy was 90.1-111.1%. The mean absolute bias of measured concentrations between multiplex and reference methods was 10.6% (range 3.0-19.9%). We developed and cross-validated a simple, accurate and precise method that allows the assay of up to 7 mAbs. Furthermore, the present method is the first to offer a simultaneous quantification of three immune checkpoint inhibitors likely to be associated in patients.
Sections du résumé
BACKGROUND
BACKGROUND
Different liquid chromatography tandem mass spectrometry (LC-MS/MS) methods have been published for quantification of monoclonal antibodies (mAbs) in plasma but thus far none allowed the simultaneous quantification of several mAbs, including immune checkpoint inhibitors. We developed and validated an original multiplex LC-MS/MS method using a ready-to-use kit to simultaneously assay 7 mAbs (i.e., bevacizumab, cetuximab, ipilimumab, nivolumab, pembrolizumab, rituximab and trastuzumab) in plasma. This method was next cross-validated with respective reference methods (ELISA or LC-MS/MS).
METHODS
METHODS
The mAbXmise kit was used for mAb extraction and full-length stable-isotope-labeled antibodies as internal standards. The LC-MS/MS method was fully validated following current EMA guidelines. Each cross validation between reference methods and ours included 16-28 plasma samples from cancer patients.
RESULTS
RESULTS
The method was linear from 2 to 100 µg/mL for all mAbs. Inter- and intra-assay precision was <14.6% and accuracy was 90.1-111.1%. The mean absolute bias of measured concentrations between multiplex and reference methods was 10.6% (range 3.0-19.9%).
CONCLUSIONS
CONCLUSIONS
We developed and cross-validated a simple, accurate and precise method that allows the assay of up to 7 mAbs. Furthermore, the present method is the first to offer a simultaneous quantification of three immune checkpoint inhibitors likely to be associated in patients.
Identifiants
pubmed: 34451893
pii: ph14080796
doi: 10.3390/ph14080796
pmc: PMC8401780
pii:
doi:
Types de publication
Journal Article
Langues
eng
Références
J Chromatogr B Analyt Technol Biomed Life Sci. 2016 Oct 1;1032:155-164
pubmed: 27296731
J Clin Chem Clin Biochem. 1984 Jun;22(6):431-45
pubmed: 6481307
Clin Cancer Res. 2013 Jul 15;19(14):3977-86
pubmed: 23741070
Clin Pharmacokinet. 2016 Nov;55(11):1381-1394
pubmed: 27312193
Eur J Cancer. 2020 Mar;128:107-118
pubmed: 32037061
Sci Rep. 2017 Jun 2;7(1):2714
pubmed: 28578404
Lancet Oncol. 2010 Feb;11(2):155-64
pubmed: 20004617
J Immunother Cancer. 2017 May 16;5:43
pubmed: 28515943
J Pharm Biomed Anal. 2017 May 30;139:30-36
pubmed: 28260630
AAPS J. 2019 Aug 20;21(6):101
pubmed: 31432293
Biomedicines. 2021 May 30;9(6):
pubmed: 34070939
Eur J Cancer. 2019 Mar;109:12-20
pubmed: 30654225
Bioanalysis. 2018 May 1;10(10):723-735
pubmed: 29771137
Ther Drug Monit. 2018 Oct;40(5):596-601
pubmed: 29847460
Clin Pharmacokinet. 2019 Jul;58(7):835-857
pubmed: 30815848
J Pharm Biomed Anal. 2019 Feb 5;164:128-134
pubmed: 30368118
J Chromatogr B Analyt Technol Biomed Life Sci. 2016 Jun 15;1023-1024:9-16
pubmed: 27155936
Clin Pharmacokinet. 2020 Mar;59(3):287-296
pubmed: 31701469
Talanta. 2021 Mar 1;224:121889
pubmed: 33379098
Br J Clin Pharmacol. 2014 Jul;78(1):106-17
pubmed: 24433434
Vaccines (Basel). 2020 Oct 31;8(4):
pubmed: 33142728
Mol Cell Proteomics. 2014 Mar;13(3):907-17
pubmed: 24443746
CPT Pharmacometrics Syst Pharmacol. 2017 Jan;6(1):29-39
pubmed: 27896938
MAbs. 2020 Jan-Dec;12(1):1795492
pubmed: 32744170
Anal Chim Acta. 2019 Aug 27;1067:63-70
pubmed: 31047150
Ann Oncol. 1998 Sep;9(9):995-1001
pubmed: 9818074
Ther Drug Monit. 2019 Aug;41(4):467-475
pubmed: 31306393
Pharmacol Res Perspect. 2021 Apr;9(2):e00757
pubmed: 33745217
J Pharm Biomed Anal. 2017 Nov 30;146:266-272
pubmed: 28888713
Clin Cancer Res. 2018 Dec 1;24(23):5841-5849
pubmed: 29891725
Ther Drug Monit. 2018 Dec;40(6):716-724
pubmed: 30048380
Ann Oncol. 2004 May;15(5):821-30
pubmed: 15111353
Br J Clin Pharmacol. 2020 Sep;86(9):1769-1777
pubmed: 32424951
Clin Cancer Res. 2011 Oct 1;17(19):6329-37
pubmed: 21953502
Lancet Oncol. 2017 May;18(5):611-622
pubmed: 28359784
Clin Biochem. 2021 Jan;87:60-66
pubmed: 33096054
Oncoimmunology. 2018 Feb 1;7(5):e1424674
pubmed: 29721387
Clin Pharmacokinet. 2010 Aug;49(8):493-507
pubmed: 20608753
Anal Chim Acta. 2018 Aug 17;1019:93-102
pubmed: 29625688
Anal Chem. 2016 Feb 2;88(3):1871-7
pubmed: 26713683
Molecules. 2021 Mar 04;26(5):
pubmed: 33806585
Transl Oncol. 2020 Jun;13(6):100771
pubmed: 32375081
Onco Targets Ther. 2017 Dec 27;11:113-121
pubmed: 29343970
J Clin Oncol. 2018 Aug 27;:JCO1800045
pubmed: 30148658
Lancet. 1986 Apr 19;1(8486):908-9
pubmed: 2870372
Cancers (Basel). 2019 Nov 13;11(11):
pubmed: 31766292
Eur J Cancer. 2020 Mar;128:119-128
pubmed: 32037060
Farm Hosp. 2020 Apr 17;44(3):81-86
pubmed: 32452306
Ann Oncol. 2002 Jun;13(6):928-43
pubmed: 12123339
Cancer Chemother Pharmacol. 2014 Apr;73(4):737-47
pubmed: 24519752
J Pharmacokinet Pharmacodyn. 2017 Oct;44(5):403-414
pubmed: 28573468
J Chromatogr B Analyt Technol Biomed Life Sci. 2021 Jan 1;1162:122489
pubmed: 33385769
Ther Drug Monit. 2010 Oct;32(5):647-52
pubmed: 20720519