Identification of potential sphingomyelin markers for the estimation of hematocrit in dried blood spots via a lipidomic strategy.

The dried blood spot (DBS) strategy is a convenient and minimally invasive approach to blood sampling. Due to its various advantages, this sampling technique has drawn significant attention in recent years. Hematocrit (HCT)-associated bias is one of the main obstacles that hinder wider DBS application in clinical practice. An accurate HCT estimation method could help calibrate HCT-associated bias and improve the quantification accuracy. This study used a lipidomics profiling strategy to identify HCT estimation markers using liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS), which provided advantages including the potential for the simultaneous measurements of target drug and HCT values. Three sphingomyelins (SMs), specifically SM 44:1, SM 44:2, and SM 44:3, were identified as potential HCT estimation markers. The proposed estimation markers were applied to 54 DBS samples collected from two sets of patients. The analytical results revealed that the estimation errors for all of the HCT values were less than 20%, which demonstrated the feasibility of using the proposed markers to estimate the HCT values for the DBS samples. We suggest that the proposed HCT markers could provide a new strategy for HCT estimation with higher convenience using an LC-ESI-MS platform, which could contribute to wider DBS applications in clinical practice. We also demonstrated that lipidomics is a promising strategy for the discovery of HCT estimation markers in DBS samples.