Quantitative bioanalysis of antibody-conjugated payload in monkey plasma using a hybrid immuno-capture LC–MS/MS approach: Assay development, validation, and a case study

Liu, Ang; Kozhich, Alexander; Passmore, David; Gu, Huidong; Wong, Richard L.; Zambito, Frank; Rangan, Vangipuram S.; Myler, Heather; Aubry, Anne‐Françoise; Arnold, Mark E.; Jian, Wang

doi:10.1016/j.jchromb.2015.08.007

Cited by 57 publications

(37 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Over the last two years, there has been some breakthroughs in developing methodology for measuring conjugated-drug for use in ADC PK. Liu et al [6] reported the assay development, validation and a case study for the quantitative bioanalysis of a conjugated-drug in cynomolgus monkey plasma using a hybrid immuno-capture, cathepsin B cleavage, LC/MS assay for a microtubule polymerization inhibitor with lysine random conjugation through a protease cleavable linker. The immuno-capture was conducted on AssayMAP streptavidin cartridge coated with the anti-idiotype capture reagent operated on an Agilent AssayMAP BRAVO system (Agilent Technologies, Wakefield, MA, USA).…”

Section: Hybrid Ligand-binding/lc-ms Assaysmentioning

confidence: 99%

Current status of antibody-drug conjugate bioanalysis

Wang¹

2017

J Appl Bioanal

Self Cite

View full text Add to dashboard Cite

Keywords: antibody-drug conjugate bioanalysis, ligand-binding assay, hybrid ligand-binding/LC-MS assay, drug-toantibody ratio Antibody-drug conjugate (ADC) consists of a cytotoxic drug covalently bound to a monoclonal antibody via a linker. Because of the complexity of ADC structure unique bioanalytical strategies are needed to identify, characterize and quantify the ADC species most relevant to safety and efficacy. ADC bioanalysis need an integrated bioanalytical approach including ligand-binding assay (LBA) and LC-MS based assays to provide comprehensive characterization of the exposure/response relationship. This mini-review will summarize recent publications on ADC bioanalytical strategies and will focus on the publications within last three years on the advancement of hybrid ligand-binding/LC-MS methods for ADC PK and stability evaluation and for intact ADC-DAR distribution measurement to profile ADC biotransformation and catabolism. Special attention is paid to the publications on selection of ADC analytes, assay platforms and DAR characteristics of LBA as well as on the transition of the bioanalytical testing strategy at different phases of clinical development.

show abstract

Section: Hybrid Ligand-binding/lc-ms Assaysmentioning

confidence: 99%

Current status of antibody-drug conjugate bioanalysis

Wang¹

2017

J Appl Bioanal

Self Cite

View full text Add to dashboard Cite

show abstract

“…Selecting the appropriate LC-MS/MS method of a large molecule largely depends on its molecular features and the required assay sensitivity or expected concentration range in the sample matrix to be analyzed. The affinity capture LC-MS and affinity capture hydrophobic interaction chromatography (HIC) methods developed for ADC characterization provide powerful tools for understanding the fate of ADCs in vivo [85].…”

Section: Lc-ms/ms and Bla Bioanalysis Of Adcsmentioning

confidence: 99%

An Overall Comparison of Small Molecules and Large Biologics in ADME Testing

Wan

2016

ADMET DMPK

View full text Add to dashboard Cite

Biologics mainly monoclonal antibodies (mAbs) and antibody-drug conjugates (ADCs) as new therapeutics are becoming increasingly important biotherapeutics. This review is intended to provide an overall comparison between small molecules (SMs) and biologics or large molecules (LMs) concerning drug metabolism and pharmacokinetic (DMPK) or associated with absorption, distribution, metabolism and elimination (ADME) testing from pharmaceutical industry drug discovery and development points of view, which will help design and conduct relevant ADME testing for biologics such as mAbs and ADCs. Recent advancements in the ADME for testing biologics and related bioanalytical methods are discussed with an emphasis on ADC drug development as an example to understand its complexity and challenges from extensive in vitro characterization to in vivo animal PK studies. General non-clinical safety evaluations of biologics in particular for ADC drugs are outlined including drug-drug interaction (DDI)and metabolite/catabolite assessments. Regulatory guidance on the ADME testing and safety evaluations including immunogenicity as well as bioanalytical considerations are addressed for LMs. In addition, the preclinical and human PK data of two marked ADC drugs (ADCETRIS, as examples are briefly discussed with regard to PK considerations and PK/PD perspectives.

show abstract

“…The biotinylation and the immunocapture procedure using streptavidin cartridges with specific biotinylated anti-Id or anti-payload capture mAb for the analysis of conjugated-payload, and the subsequent cathepsin-B cleavage and LC-MS/MS detection have been described in details elsewhere [33].…”

Section: Lb-lc-ms/ms Hybrid Assays For Conjugatedpayloadmentioning

confidence: 99%

“…Affinity-capture followed by capillary LC-MS or hydrophobic interaction chromatography (HIC) to characterize intact ADC DAR distribution in biological matrices have been reported [10,[29][30][31][32]. Immunocapture combined with cathepsin-B cleavage followed by LC-MS/MS for the quantitation of conjugated-payload has been discussed [9,10] and a case study of assay development, validation, and application has been published [33]. A recent publication reports a protein A capture LC-MS/MS hybrid assay with papain (a cysteine protease) cleavage for the quantitation of valine-citrullin-linked MMAE ADCs [34].…”

mentioning

confidence: 99%