AI Article Synopsis
- * Results showed that two MS methods for quantifying the unconjugated drug had similar detection limits of 0.030 and 0.015 ng/ml, respectively, ensuring reliable measurements.
- * It was found that the drug-to-antibody ratio for ADCs with engineered glutamine linkers remained stable over three weeks, while those with cysteine linkers decreased from four to three over two weeks, highlighting the significance of linkers in ADC stability.
Article Abstract
Aim: The application of high-resolution MS to antibody-drug conjugate (ADC) drug development may provide insight into their safety and efficacy. Quantification of unconjugated cytotoxic drug (payload) and characterization of drug-to-antibody ratio distribution were determined in plasma using orthogonal acceleration quadrupole-time-of-flight MS.
Results: Unconjugated payload quantification determined by quadrupole-time-of-flight-based MRM(highresolution) and triple quadrupole-based multiple reaction monitoring were comparable and achieved detection limits of 0.030 and 0.015 ng/ml, respectively. As determined by immunocapture and TOF-MS, drug-to-antibody ratio remained unchanged up to 3-weeks postdose for an ADC containing engineered glutamine linkers, but declined from four to three over 2 weeks in an ADC containing engineered cysteine linkers.
Conclusion: The use of high-resolution MS in ADC drug discovery confirms its utility within the bioanalytical discipline.
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| http://dx.doi.org/10.4155/bio-2016-0120 | DOI Listing |
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