Abstract: Methods, compositions, kits, and apparatuses for MS-based quantification of a target analyte (e.g., a peptide, a hormone) in a sample are provided for increasing the productivity and/or throughput of samples by reducing the time and/or cost associated with conventional techniques for external instrument calibration that typically utilize a series of calibrators that are sequentially run through the same analytical process as a batch of samples. In various aspects, calibration mixtures are provided containing a known quantity of a plurality of calibrants for a target analyte of interest, with each calibrant being distinguishable in the calibration mixture by mass spectrometry such that a complete calibration curve can be generated from a single external calibration run.