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Microsampling Assays for Pharmacokinetic Analysis and Therapeutic Drug Monitoring of Antimicrobial Drugs in Children: A Critical Review.

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PURPOSE With the increasing prevalence of multi-drug resistant organisms, therapeutic drug monitoring (TDM) has become a common tool for assuring the safety and efficacy of antimicrobial drugs at higher doses.… Click to show full abstract

PURPOSE With the increasing prevalence of multi-drug resistant organisms, therapeutic drug monitoring (TDM) has become a common tool for assuring the safety and efficacy of antimicrobial drugs at higher doses. Microsampling techniques, including dried blood spotting (DBS) and volumetric absorptive microsampling (VAMS), are attractive tools for TDM and pediatric clinical research. For microsampling techniques to be a useful tool for TDM, it is necessary to establish the blood-plasma correlation and the therapeutic window of antimicrobial drugs in the blood. METHODS DBS involves the collection of small volumes of blood (30 - 50 µL per spot) on a filter paper, while VAMS allows the accurate and precise collection of a fixed volume of blood (10-30 µL) with microsampling devices. One of the major advantages of VAMS is that it reduces or eliminates the volumetric blood hematocrit (HCT) bias associated with DBS. Liquid chromatography with tandem mass spectrometry (LC-MS/MS) is a powerful tool for the accurate quantification of antimicrobial drugs from small volumes of blood specimens. RESULTS This review summarizes the recent LC-MS/MS assays that have employed DBS and VAMS approaches for quantifying antimicrobial drugs. Sample collection, extraction, validation outcomes, including the inter- and intra-assay accuracy and precision, recovery, stability, and matrix effect, as well as the clinical application of these assays and their potential as tools of TDM are discussed herein. CONCLUSION Microsampling techniques, such as VAMS, provide an alternative approach to traditional plasma sample collection for TDM.

Keywords: blood; antimicrobial drugs; therapeutic drug; collection; drug monitoring

Journal Title: Therapeutic Drug Monitoring
Year Published: 2020

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