Despite the various approaches currently available for ADC quantification, LCMS-based bioanalytical challenges still remain, especially for ADCs with linkers that cannot be enzymatically cleaved. In such cases, conjugated payload from ADCs can be analyzed at intact or subunit levels by LC-HRMS. 5-7 However, it is typically limited by low sensitivity and low throughput due to the complex and time-consuming data deconvolution process, which could be burdensome to support bioanalysis of large studies. Furthermore, the conventional enzyme release of payload approach may not be suitable for the analysis of ADC biotransformation due to structural changes of payload, or linker. Besides that, payload may be released from non-cleavable linker chemically and measured by LC-MS. 9 However, it depends on the chemical structure of the linker-payload and requires bespoke methodology that cannot be directly applied to other cases.