Practice-Oriented Quality Specifications for Therapeutic Drug Monitoring

To the Editor: The introduction of biological criteria has transformed quality control from descriptive process statistics to control of fulfillment of quality requirements on the basis of normally observed biological variation of analytes (1). Because drugs are xenobiotic, it is difficult to determine “biological” variation. Quality requirements remain contingent on achievable instrument performance, in the most optimistic case based on best practice criteria, or on arbitrary rules. An article by Fraser, published in 1987 (2), tried to address this gap (3, 4). Fraser estimated the biological variation for the drug concentration on the basis of fundamental pharmacokinetic theory, assuming a first order kinetics of elimination, rapid absorption as compared to elimination, a single compartmental system, and constant half-life and dosing regimens. For drugs with >2 …