MSACL 2016 EU Abstract

Estimation and Correction of the Blood Volume Variations of Dried Blood Spots Using a Postcolumn Infused-internal Standard Strategy with LC-ESI-MS

Hsiao-Wei Liao (Presenter)
School of Pharmacy, National Taiwan University

Bio: My name is Hsiao-Wei Liao, I am a postdoctoral researcher in School of Pharmacy, College of Medicine, National Taiwan University in Taiwan. My research mainly focuses on the development of the bioanalysis method for clinical use such as therapeutic drug monitoring, pharmaceutical analysis, lipidomics, and metabolomics.

Authorship: Hsiao-Wei Liao (1,2), Shu-Wen Lin (3), Guan-Yuan Chen (1,2)), and Ching-Hua Kuo (1,2)
(1)School of Pharmacy, College of Medicine, National Taiwan University (2)The Metabolomics Core Laboratory, Center of Genomic Medicine, National Taiwan University (3)Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University

Short Abstract

Dried blood spot (DBS) is considered a promising technique in advancing personalized medicine. Whole-spot extraction is advantageous because it is less affected by HCT-caused bias, but blood volume variation limits the use of this sample processing technique. This study proposed a novel approach using the postcolumn infused-internal standard (PCI-IS) method for correcting the blood volume variation on DBS samples. The PCI-IS method utilized the isotonic property of blood samples, by evaluating the extent of the ion suppression at the first significant ion suppression zone, the blood volume on the DBS cards can be calculated.

Long Abstract

Dried blood spots (DBSs) have had a long history in disease screening in newborns but have gained attention in recent years in the medical care of adults because of the growing importance of personalized medicine. DBSs have several advantages, such as easy transportation, cost-effectiveness and minimally invasive biological sampling. There are two strategies to process DBS samples. One method takes a fixed diameter of subsample, and another requires the extraction of the whole-spot. The whole-spot extraction method is less affected by hematocrit-caused errors, but it requires calibration of the blood volume. We propose a novel strategy using a postcolumn infused-internal standard (PCI-IS) method with liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS) for estimating and correcting blood volume variations on the DBS cards. By using PCI-IS to measure the extent of ion suppression in the first ion suppression zone in the chromatogram, the blood volume on the DBS cards can be calculated and further calibrated. We used reference blood samples with different volumes (5 to 25 µL) to construct a calibration curve between the blood volume and the extent of ion suppression. The calibration curve was used to estimate the blood volume on the DBS cards collected from 6 volunteers, with 5 designated volumes from each volunteer. The estimation accuracy of the PCI-IS method was between 74.5 to 120.3%. The validated PCI-IS method was used to estimate and calibrate blood volume variation and also to quantify the voriconazole concentration for 26 patients undergoing voriconazole therapy. A high correlation was found for the quantification results between the DBS samples and the conventionally used plasma samples (r=0.97). The PCI-IS method was demonstrated to be a simple and accurate method for estimating and calibrating the blood volume variation on DBS cards, which greatly facilitates using the DBS method for therapeutic drug monitoring (TDM) for improving the efficacy and safety of drug therapy.


References & Acknowledgements:

This study was supported by the Ministry of Science and Technology of Taiwan (MOST 104-2113-M-002-009-). The authors thank the NTU Integrated Core Facility for Functional Genomics of National Research Program for Genomic Medicine of Taiwan for their technical assistance.


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