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      Dried Blood Spots for Global Health Diagnostics and Surveillance: Opportunities and Challenges

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          Abstract.

          There is increasing interest in using dried blood spot (DBS) cards to extend the reach of global health and disease surveillance programs to hard-to-reach populations. Conceptually, DBS offers a cost-effective solution for multiple use cases by simplifying logistics for collecting, preserving, and transporting blood specimens in settings with minimal infrastructure. This review describes methods to determine both the reliability of DBS-based bioanalysis for a defined use case and the optimal conditions that minimize pre-analytical sources of data variability. Examples by the newborn screening, drug development, and global health communities are provided in this review of published literature. Sources of variability are linked in most cases, emphasizing the importance of field-to-laboratory standard operating procedures that are evidence based and consider both stability and efficiency of recovery for a specified analyte in defining the type of DBS card, accessories, handling procedures, and storage conditions. Also included in this review are reports where DBS was determined to not be feasible because of technology limitations or physiological properties of a targeted analyte.

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          Most cited references134

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          Strategies for the assessment of matrix effect in quantitative bioanalytical methods based on HPLC-MS/MS.

          In recent years, high-performance liquid chromatography (HPLC) with tandem mass spectrometric (MS/MS) detection has been demonstrated to be a powerful technique for the quantitative determination of drugs and metabolites in biological fluids. However, the common and early perception that utilization of HPLC-MS/MS practically guarantees selectivity is being challenged by a number of reported examples of lack of selectivity due to ion suppression or enhancement caused by the sample matrix and interferences from metabolites. In light of these serious method liabilities, questions about how to develop and validate reliable HPLC-MS/MS methods, especially for supporting long-term human pharmacokinetic studies, are being raised. The central issue is what experiments, in addition to the validation data usually provided for the conventional bioanalytical methods, need to be conducted to confirm HPLC-MS/MS assay selectivity and reliability. The current regulatory requirements include the need for the assessment and elimination of the matrix effect in the bioanalytical methods, but the experimental procedures necessary to assess the matrix effect are not detailed. Practical, experimental approaches for studying, identifying, and eliminating the effect of matrix on the results of quantitative analyses by HPLC-MS/MS are described in this paper. Using as an example a set of validation experiments performed for one of our investigational new drug candidates, the concepts of the quantitative assessment of the "absolute" versus "relative" matrix effect are introduced. In addition, experiments for the determination of, the "true" recovery of analytes using HPLC-MS/MS are described eliminating the uncertainty about the effect of matrix on the determination of this commonly measured method parameter. Determination of the matrix effect allows the assessment of the reliability and selectivity of an existing HPLC-MS/MS method. If the results of these studies are not satisfactory, the parameters determined may provide a guide to what changes in the method need to be made to improve assay selectivity. In addition, a direct comparison of the extent of the matrix effect using two different interfaces (a heated nebulizer, HN, and ion spray, ISP) under otherwise the same sample preparation and chromatographic conditions was made. It was demonstrated that, for the investigational drug under study, the matrix effect was clearly observed when ISP interface was utilized but it was absent when the HN interface was employed.
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            Therapeutic Drug Monitoring by Dried Blood Spot: Progress to Date and Future Directions

            This article discusses dried blood spot (DBS) sampling in therapeutic drug monitoring (TDM). The most important advantages of DBS sampling in TDM are the minimally invasive procedure of a finger prick (home sampling), the small volume (children), and the stability of the analyte. Many assays in DBS have been reported in the literature over the previous 5 years. These assays and their analytical techniques are reviewed here. Factors that may influence the accuracy and reproducibility of DBS methods are also discussed. Important issues are the correlation with plasma/serum concentrations and the influence of hematocrit on spot size and recovery. The different substrate materials are considered. DBS sampling can be a valid alternative to conventional venous sampling. However, patient correlation studies are indispensable to prove this. Promising developments are dried plasma spots using membrane and hematocrit correction using the potassium concentration.
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              Dried blood spot methods in therapeutic drug monitoring: methods, assays, and pitfalls.

              This article reviews dried blood spot (DBS) sampling in therapeutic drug monitoring. The DBS method involves applying whole blood obtained via a fingerprick to a sampling paper. After drying and transportation, the blood spot is extracted and analyzed in the laboratory. Assays of many medicines in DBS have already been reported in the literature and are reviewed here. The technique involved in and factors that may influence the accuracy and reproducibility of DBS methods are also discussed. DBS sampling ultimately seems to be a useful technique for therapeutic drug monitoring that could have many advantages in comparison with conventional venous sampling. However, its benefits must be weighed against the degree of potential errors introduced via the sampling method; there is evidently a need for more standardization, quality assurance, basic research, and assay development.
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                Author and article information

                Journal
                Am J Trop Med Hyg
                Am. J. Trop. Med. Hyg
                tpmd
                tropmed
                The American Journal of Tropical Medicine and Hygiene
                The American Society of Tropical Medicine and Hygiene
                0002-9637
                1476-1645
                August 2018
                02 July 2018
                02 July 2018
                : 99
                : 2
                : 256-265
                Affiliations
                [1]Global Health Division, Bill & Melinda Gates Foundation, Seattle, Washington
                Author notes
                [* ]Address correspondence to Mark D. Lim, Global Health Division, Bill and Melinda Gates Foundation, Seattle, WA 98102. E-mail: markdlim@ 123456gmail.com

                Author’s address: Mark D. Lim, Bill & Melinda Gates Foundation, Seattle, WA, E-mail: markdlim@ 123456gmail.com .

                Article
                tpmd170889
                10.4269/ajtmh.17-0889
                6090344
                29968557
                69bcaab9-c145-400a-81fa-d067cde2fd26
                © The American Society of Tropical Medicine and Hygiene

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 15 November 2017
                : 02 May 2018
                Page count
                Pages: 10
                Categories
                Review Article

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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