Dried blood spot analysis without dilution: Application to the LC–MS/MS determination of BMS-986001 in rat dried blood spot

• A no-dilution strategy was used for LC–MS/MS quantitation of BMS-986001 in rat DBS.
• An assay with a linear range of 5 orders of magnitude for BMS-986001 was developed.
• The assay was validated and successfully used to support a toxicology study in rats.
• The DBS concentration data agreed well with the plasma data for the rat study.
• First report of using this strategy for analysis of DBS samples in a real study.

Sample dilution is one major challenge in dried blood spot (DBS) bioanalysis. To resolve this issue, we applied a no-dilution strategy for DBS analysis by using a calibration curve with very wide linear range. We developed an LC–MS/MS DBS assay with a linear range of 5 orders of magnitude (50–5000,000 ng/mL) for BMS-986001, an HIV drug under development, by simultaneously monitoring two selective reaction monitoring transitions of different intensity. The assay was validated and successfully applied to the analysis of DBS samples collected in a toxicology study in rats dosed with BMS-986001. All samples were analyzed without any dilution. We also compared the concentration data generated from the DBS method and a validated plasma assay for the same study. The two sets of data agreed well with each other, demonstrating the validity of this strategy for DBS analysis. This approach provides an effective and convenient way to eliminate complicated dilution for DBS and other sample collection techniques.