Evidence map›Paper›PMID 30848315›Full record

ArticleAnalytical and bioanalytical chemistry2019

Application of triple quadrupole mass spectrometry for the characterization of antibody-drug conjugates.

Malin Källsten, Matthijs Pijnappel, Rafael Hartmann, Fredrik Lehmann, Lucia Kovac, Sara Bergström Lind, Jonas Bergquist

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Analytical and bioanalytical chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
1.4field-weighted citation impact, top 19% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed, 8 citations in OpenAlex.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 1 country.

Malin KällstenDepartment of Chemistry-BMC, Analytical Chemistry, Uppsala University, Box 599, 751 24, Uppsala, Sweden. malin.kallsten@kemi.uu.se.
Matthijs PijnappelRecipharm OT Chemistry AB, Virdings allé 32b, 754 50, Uppsala, Sweden.
Rafael HartmannDepartment of Medicinal Chemistry, Organic Pharmaceutical Chemistry, Uppsala Biomedical Center, Uppsala University, Box 574, 751 23, Uppsala, Sweden.
Fredrik LehmannOncopeptides AB, Luntmakargatan 46, SE-111 37, Stockholm, Sweden.
Lucia KovacRecipharm OT Chemistry AB, Virdings allé 32b, 754 50, Uppsala, Sweden.
Sara Bergström LindDepartment of Chemistry-BMC, Analytical Chemistry, Uppsala University, Box 599, 751 24, Uppsala, Sweden.
Jonas BergquistDepartment of Chemistry-BMC, Analytical Chemistry, Uppsala University, Box 599, 751 24, Uppsala, Sweden. jonas.bergquist@kemi.uu.se.
Uppsala University · SERecipharm (Sweden) · SEOncopeptides (Sweden) · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Antibody-drug conjugates (ADCs) are an inherently heterogeneous class of biotherapeutics, the development of which requires extensive characterization throughout. During the earliest phases of preclinical development, when synthetic routes towards the desired conjugate are being assessed, the main interest lies in the determination of the average drug-to-antibody ratio (DAR) of a given batch as well as information about different conjugation species. There has been a trend in mass spectrometry (MS)-based characterization of ADCs towards the use of high-resolving mass spectrometry for many of these analyses. Considering the high cost for such an instrument, the evaluation of cheaper and more accessible alternatives is highly motivated. We have therefore tested the applicability of a quadrupole mass analyzer for the aforementioned characterizations. Eight ADCs consisting of trastuzumab and varying stoichiometries of Mc-Val-Cit-PABC-monomethyl auristatin E conjugated to native cysteines were synthesized and served as test analytes. The average DAR value and molecular weights (Mw) of all detected chains from the quadrupole mass analyzer showed surprisingly high agreement with results obtained from a time-of-flight (TOF) mass analyzer and hydrophobic interaction chromatography (HIC)-derived values for all investigated ADC batches. Acquired Mw were within 80 ppm of TOF-derived values, and DAR was on average within 0.32 DAR units of HIC-derived values. Quadrupole mass spectrometers therefore represent a viable alternative for the characterization of ADC in early-stage development. Graphical abstract.

Indexed as

Antineoplastic Agents, ImmunologicalChromatography, Reverse-PhaseCysteineHydrophobic and Hydrophilic InteractionsImmunoconjugatesLimit of DetectionMass SpectrometryMolecular WeightSpectrophotometry, UltravioletTrastuzumabAntineoplastic Agents, ImmunologicalCysteineImmunoconjugatesTrastuzumabAntibody–drug conjugatesDrug-to-antibody ratioReversed-phase liquid chromatographyTriple quadrupole mass spectrometry

Identifiers

PMID30848315
PMCPMC6470114
OpenAlexW2921753159

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.