Interference Testing and Isobaric Compounds: Is Your Mass Spectrometry-based Assay as Good as You Think It Is?

The use of urine drug tests to monitor a patientu0027s adherence to prescribed opioid use in pain management is recommended by numerous clinical practice guidelines (1). Traditionally, these tests have been done using urine immunoassays, which suffer from a lack of sensitivity and specificity. New Laboratory Medicine Practice Guidelines (LMPG)2 from the American Association for Clinical Chemistry (AACC) Academy (executive summary published in this special issue) actually recommend first-line definitive (e.g., mass spectrometry-based) urine drug testing because it overcomes the limitations of immunoassays. Although mass spectrometry-based (MS) methods are often referred to as the “gold standard” and are used routinely in the therapeutic drug monitoring of many medications, several challenges such as matrix interference or isobaric compounds exist. Each of these items must be acknowledged and specifically addressed during validation before implementing any MS-based test in a clinical laboratory.To illustrate some of these items, the …