The invention provides methods, assays and systems for determining the efficacy of a TEC family kinase inhibitor on a target kinase. The methods, assays and systems relate to determining the occupancy of a target kinase by a TEC family kinase inhibitor (e.g., BTK inhibitors). Such quantitative measurements are used to inform therapeutic treatment and the over-all health care management of a subject. For example, diagnostic kits for diagnosing, prognosing, and monitoring a disease or indication benefitting from treatment with a TEC family kinase inhibitor are provided. In another example, diagnostic kits for identifying responders to TEC family kinase inhibitor therapy, determining therapeutic regimens, and detecting resistance to TEC family kinase inhibitor also are provided.
