Journal
ANALYTICAL CHEMISTRY
Volume 89, Issue 9, Pages 5115-5123Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.analchem.7b00688
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We demonstrate a novel strategy using affinity extraction (AE) LC-MS to directly measure drug exposure and target engagement, two, critical pharmacological questions, with a 'single'assay. The assay measures total drug and target concentration :at the;i-site of therapeutic action, as well as the amount of target bound to drug. The case study presented applies the strategy to measure drug engagement of a membrane bound receptor (CD40) that is critical to immune regulation in colon biopsies collected from monkey dosed with an anti-CD40 antibody. Unlike other techniques that measure receptor occupancy, such as flow cytometry, this technique does hot rely on-viable cells allowing measurement of frozen samples in a remote setting from the clinic.
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