Application Note: Sensitive quantitation of the ADC ado-trastuzumab emtansine free cytotoxic drug DM1 in serum using MicroLC-MS
Antibody-drug conjugates (ADC’s) are targeted cancer therapeutics that deliver a cytotoxic agent, the payload, to the tumour.
For a good understanding of the pharmacokinetics of these drugs, it is important to quantitate not only the antibody, but also the amount of released payload in plasma/serum upon drug administration. ELISA based methods have been used for quantitation, but recently there has been interest in using liquid chromatography- tandem mass spectrometry (LC-MS/MS) methods because of its high selectivity, accuracy, and precision. Especially for Drug Metabolism and Pharmacokinetics (DMPK) studies involving small animals, sensitivity is critical because of the limited volume of sample available. Previously, see Table 1, we have demonstrated improved sensitivity of up to five fold for the quantitation of the ADC Ado-Trastuzumab Emtansine1 and the Antibody Infliximab2 with trap-and elute microflow LC in plasma when compared to using conventional analytical LC-MS/MS. In this presentation we describe the use of Microflow LC for the LC-MS/MS analysis of the payload Emtansine (DM1) of the ADC Ado-trastuzumab Emtansine.
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