Matrix effects in therapeutic drug monitoring surveys. Proposed protocol to identify error components and quality improvement opportunities.
Therapeutic drugs are not endogenous compounds. Therefore, differing reactivities between proficiency testing and patient samples have potential mechanisms beyond those attributable to alterations of the serum protein base, stabilizing materials, and other manufacturing components. The therapeutic drug monitoring proficiency sample is the ultimate in polypharmacy. Cross-reactivities may be uncovered that may or may not occur with any frequency in patient samples. Drugs are present in therapeutic drug monitoring proficiency samples in the absence of their metabolites, which may alter interactions with the assay systems. The CAP Therapeutic Drug Monitoring Resource Committee has contacted manufacturers when a specific method yields proficiency test results that differ from all other methods and/or the weighed-in target values. Only a few examples have been formally evaluated with the "matrix evaluation protocol." The protocol is very useful and has identified some matrix effects. A protocol is proposed using multiple samples containing survey base material. Data analysis using reciprocal plots will identify interference and corroborate calibration or recovery errors in the presence of survey base material. Data from 1987 through 1991 surveys for lithium and theophylline illustrate this data analysis and show interference from other drugs and suggest calibration errors. Weighted-in target values are the most rigorous method to provide accurate, transferable patient results and convince ourselves and our evaluators that we know what we are measuring. All of us need to be committed to improvement of laboratory procedures. I believe weighed-in target values are the appropriate and achievable goal for proficiency testing the majority of therapeutic drug monitoring analytes. Implementation of target values requires diligent and intricate collaboration among laboratorians, surveyors, manufacturers, and regulators.
Witte
D L
DL
Ottumwa Regional Health Foundation, Iowa City, Iowa.
D015982:Bias; D002624:Chemistry, Clinical / Q000592:standards*; D003625:Data Collection; D016903:Drug Monitoring / Q000592:standards*; D006801:Humans; D008094:Lithium / Q000097:blood; D011786:Quality Control; D012015:Reference Standards; D012044:Regression Analysis; D012459:Salicylates / Q000097:blood; D020156:Salicylic Acid; D013806:Theophylline / Q000097:blood
D012459:Salicylates; D008094:Lithium; D013806:Theophylline; D020156:Salicylic Acid