Review of the Preanalytical Errors That Impact Therapeutic Drug Monitoring

Abstract

Purpose: Preanalytical errors comprise the majority of testing errors experienced by clinical laboratories and significantly impact the accuracy of therapeutic drug monitoring (TDM).Methods: Specific preanalytical factors in sample timing, collection, transport, processing, and storage that lead to errors in TDM were reviewed. We performed a literature search using several scientific databases including PubMed, ScienceDirect, Scopus, Web of Science, and ResearchGate for human studies published in the English language from January 1980 to February 2021, reporting on TDM and the preanalytical phase.Results: Blood collection errors (ie, wrong anticoagulant/clot activator used, via an intravenous line, incorrect time after dosing) delay testing, cause inaccurate results, and adversely impact patient care. Blood collected in lithium heparin tubes instead of heparin sodium tubes produce supertoxic lithium concentrations, which can compromise care. Specimens collected in serum separator gel tubes cause falsely decreased concentrations due to passive absorption into the gel when samples are not processed and analyzed quickly. Dried blood spots are popular for TDM as they are minimally invasive, allowing for self-sampling and direct shipping to a clinical laboratory using regular mail. However, blood collection techniques, such as trauma to the collection site, filter paper fragility, and hematocrit (Hct) bias, can adversely affect the accuracy of the results. Volumetric absorptive microsampling is a potential alternative to dried blood spot that offers fast, volume-fixed sampling, low pain tolerance, and is not susceptible to Hct concentrations. Conclusions:The identification of preanalytical factors that may negatively impact TDM is critical. Developing workflows that can standardize TDM practices, align appropriate timing and blood collection techniques, and specimen processing will eliminate errors.

Behind the Curtain: Therapeutic Drug Monitoring of Psychotropic Drugs from a Laboratory Analytical Perspective

“…76 Typically, blood sampling from an intravenous line should be avoided. Therefore, if drugs are administered intravenously, 79 blood samples for TDM should not be collected from the same intravenous line. Drug contamination may lead to high drug concentrations.…”

Therapeutic Drug Monitoring of Antibiotic Drugs: The Role of the Clinical Laboratory

“…54 Care should be taken to prevent specimen contamination by the infusion solution, which would lead to erroneous results and possible misinterpretation. 53…”

“…54 Care should be taken to prevent specimen contamination by the infusion solution, which would lead to erroneous results and possible misinterpretation. 53 The second critical issue is the processing and storage of specimens, which is particularly true for aminoglycoside testing and analyses of some members of the beta-lactam family. Appropriate storage times under different conditions reported in manufacturer documents or the literature are provided in Table 3.…”

“…In general, in critically ill patients receiving infusion therapy, sample collection within the last 30 minutes before the next dosing to monitor C min , 30 minutes after the end of infusion for C max , and at any time point during the continuous infusion at steady-state (>4 half-life times after initiation) for Css is appropriate. 53 For area under the curve–based monitoring, collecting 2 samples is generally required, with the exact times depending on the drug and the locally applied protocol. Some practical recommendations are provided in the recently published position paper on antimicrobial TDM in critically ill adult patients.…”

“…The effects of multiple preanalytical factors on the quality of laboratory results are well established. 53 Along with proper specimen collection, adequate centrifugation, and suitable specimen collection tubes, 2 additional aspects of particular importance need to be considered for antibiotic TDM.…”