An additional problem with the use of synthetic reference peptides or protein is the absence of analyte-free matrix for preparation of calibration curves. In respect to all abovementioned concerns about the commutabilily of synthetic peptide or protein reference standards, matrix-based, native, and value-assigned, proien calibrators will provide most reliable absolute quantization of endogenous protien. Because the protein standards are subjected to a work-up that is identical to that of the unknown samples, they are likely to correct for any variability in the (pre-) analytical work-flow. The use of a (single-point) matrix-based human plasma external calibrator has, for example, shown to be effective for the quantitation of apolipoprotiens. Obviously, absence of matrix-effects has to be assured before native protein calibrators can be used as (commutable) reference materials.