1. A method for generating a net analyte signal calibration model for use in detecting an analyte in a test subject, comprising: a) providing a set of in vivo infrared spectra for a test subject during a period in which an analyte concentration is essentially constant; b) calculating an optimal subspace of spectra that at least substantially describes all non-analyte dependent spectral variance in the in vivo spectra of step a); c) providing a pure component infrared spectrum for the analyte; and d) calculating a net analyte signal spectrum from a data set comprising the optimal subspace spectra of b) and the pure analyte spectrum of c), wherein the net analyte signal spectrum identifies one or more in vivo spectral features specific to the analyte.