Abstract
Background: Antibody-drug conjugates (ADCs) are a promising modality for cancer treatment; however, considering their complicated nature, analytical complexity in understanding their pharmacokinetics and pharmacodynamics in the body presents a significant challenge. Results: Vorsetuzumab maleimidocaproyl valine-citrulline p-aminobenzyloxycarbonyl monomethyl auristatin E was used to develop pretreatment and analytical workflows suitable for ADCs. Monomethyl auristatin E release and drug-to-antibody ratio retention were consistent in mouse plasma but inconsistent in monkey and human plasma. Further, metabolites were species-specific. Microflow-liquid chromatography/high-resolution mass spectrometry (LC-HRMS) resulted in a 4-7-fold improvement in detection sensitivity compared with conventional flow LC-HRMS. Conclusion: Microflow-LC-HRMS can be a useful tool in understanding the complex properties of ADCs in the body from a drug metabolism and pharmacokinetics point of view.
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