Three different analysis platforms using LC-MS were successfully developed for pharmacokinetic (PK) studies of an antibody drug in serum. These analysis platforms can be selectively used for different types of protein drugs, which ranged from a very specific for a particular drug (antibody enrichment) to a less specific for any antibody drugs with an Fc domain (protein A enrichment), and to a very generic method that can be used for any protein drugs (albumin depletion method). In this manner, the three platforms will be applicable to a wide range of antibody therapeutic studies for different species. The analysis using an albumin depletion method (with sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE)) achieved the detection of the drug (to 1 ng) in an aliquot of serum (30 microL) with a 5-order magnitude of linearity. The analysis using protein A enrichment (with SDS-PAGE) achieved the detection of the drug at a 50-fold lower level (to 0.02 ng). Without the use of SDS-PAGE for separation, the use of protein A enrichment achieved the detection to 10 ng and using the antidrug antibody enrichment achieved the detection to 0.1 ng, with a similar linear dynamic range. These three analysis platforms produced good agreement with a mimic PK study of the drug in monkey serum, as compared to the enzyme-linked immunosorbent assay (ELISA) approach. In addition, these analysis platforms can be selectively applied for PK studies of drugs with different requirements of development time and resources. Such as, the antibody enrichment method can be used in a high-throughput manner but limited to a specific protein drug only. On the other hand, the albumin depletion method can be applied to many types of protein drugs but with the laborious sample preparation steps (SDS-PAGE and the subsequent in-gel digestion). When antidrug antibodies are not available for antibody drugs or the sensitivity requirement is not stringent (e.g., >10 ng), using protein A enrichment (without using SDS-PAGE) seems to be a good choice for PK studies which require fast throughput.