Measurement of insulin has been identified as a paramount metric for specific clinical research, therapeutic development, forensic and sports doping applications. Conventional assays are plagued by the simple inability to differentiate endogenous from insulin analogs. While LC-MS has demonstrated the ability to overcome this shortcoming, these methods have lacked analytical sensitivity demanded by the field. Complicated by the presence of high plasma background, selective sample interface workflows are required for proper LC-MS detection/quantification. To satisfy all the listed capabilities, a Mass Spectrometric Immunoassay (MSIA) method was developed for the highthroughput, highly analytically sensitive quantification of insulin and its analogs from human donor plasma for clinical research.