Assay interference caused by common drugs is a challenging and often overlooked problem. Dr. Pradip Datta has written a brief blog discussing drugs as potential interferents in clinical assays. We think you will find his insights interesting and thought provoking. With the thousands of drugs in the marketplace, how can manufacturers and laboratorians recognize and test the drugs that may affect their assays?
Sun Diagnostics is now offering a test kit to help assess potential drug interferents. The kit includes drugs that were recommended by an expert panel as “…likely to present frequent, clinically significant interference.” There are many newer over-the-counter and prescription drugs that may also be potential interferents, but the drugs recommended by the expert panel, packaged in a convenient kit, represent a great first step in addressing this unmet need for better drug interference testing.
Testing Interference from Common Drugs
Pradip Datta, PhD
Interference from commonly used drugs in laboratory tests is a major problem for both manufacturers and end-users of in-vitro diagnostic assays. The drugs can be common over the counter drugs (analgesics, antihistamines or anti-inflammatory agents), or prescribed medications (antibiotics, anticancer, neurologic); some of the latter are prescribed for lifetime usage (for example, anti-asthmatic, cholesterol-lowering, immunosuppressant, etc.). Such interference affects not only immunoassays (by cross-reactivity), but also chemistry assays (by enzyme interference or chromogenic side reactions). Serious errors in reported results may happen without knowledge of such interference. Manufacturers of commercial diagnostic assays may report some such interference in their assay Inserts. But with some 20,000 drugs approved by FDA and an average of 340 new drugs entering the formulary every year, it is a formidable task to study the drug interference of a new assay. As with any interference, the effect becomes more prominent and critical at low analyte levels; and with increasing emphasis on the clinical utility of very low endogenous concentrations of some analytes like cardiac troponin or prostate specific antigen (PSA), this problem will get worse. An additional difficulty in evaluating drug interference is the possibility of interference from drug metabolites as well.
Sonntag and Scholer1 observed a variety of interference (positive or negative) from 18 common drugs in some 70 assays. There is a larger compendium of >40,000 drug effects on laboratory tests2. In recognition of the problem of interference, the Clinical and Laboratory Standards Institute (CLSI) developed a protocol to study interference in any assay before adopting it in the laboratory3. The protocol measures both positive and negative assay interferences.
In addition to therapeutic drugs, laboratorians must evaluate effects of abused drugs as well in a new assay. The commonest drug of abuse (DAU) is ethanol. With increasing recognition of chronic pain as a debilitating disease, abuse or misuse of pain medications is a growing problem.
Every clinical laboratory should be aware of the potential of drug interference, especially from the drugs prevalent in the population they serve, and be careful in reporting their results. It is easier to spot an aberrant result outside the reference range of the assay, but more difficult when the interference has the opposite effect: causing a clinically important result to fall inside the reference range. Knowledge of patient’s drug history and drug interference will help the laboratorian in such cases.
- Sonntag O, Scholer A. Drug interference in clinical chemistry: recommendations of drugs and their concentrations to be used in drug interference studies. Ann Clin Biochem 2001; 38:376-385.
- Young DS. Effects of drugs on clinical laboratory tests, 5th ed. Washington: AACC Press, 2000.
- Clinical and Laboratory Standards Institute (CLSI). CLSI document EP7-A2 (ISBN 1-56238-584-4). Clinical and Laboratory Standards Institute, 940 West Valley Road, Suite 1400, Wayne, Pennsylvania 19087-1898 USA, 2005.