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Updated: Sep 23, 2025

Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses
Published on: August 30, 2018
A suspected case of falsely low digoxin and vancomycin concentrations caused by free kappa light chains with PETINIA
Nga Yeung Tang1,2, Kelly Walewski1, Robin Carey-Ballough1
1Department of Pathology and Laboratory Medicine, Beaumont Health, Royal Oak, MI, USA.
Abstract:
Vancomycin and digoxin are associated with potential toxicity and serum concentrations need to be monitored in certain patients. Previous reports suggested IgM paraproteins could interfere with vancomycin assays, and no paraprotein interference has been reported with digoxin assays. Here we present a suspected case of free-kappa light chains-mediated falsely low digoxin and vancomycin concentrations with Abbott particle-enhanced turbidimetric inhibition immunoassay (PETINIA) method. A 53-year-old patient received multiple doses of vancomycin and digoxin intravenously, but trough vancomycin and random digoxin concentrations repeatedly measured as <1.1 μg/mL and <0.2 ng/mL respectively with Abbott PETINIA method. Results from alternative methods showed concentrations reaching toxic levels and administration of the drugs was immediately terminated. A significantly elevated level of free-kappa light chains, possibly in polymeric form as suggested by protein electrophoresis result, was suspected to be the cause of falsely low results. During the laboratory investigation, absorbance curves revealed increased agglutination in the patient's samples in the latter part of the reaction, suggesting interfering substances led to production of turbidity after reagents were added. Protein-free filtration partially recovered the drugs with Abbott PETINIA. When drug concentrations do not correlate with clinical judgment, clinicians and pharmacists should consult clinical laboratories for investigation of potential interfering substances.
Insights
Free kappa light chains can cause falsely low measurements of vancomycin and digoxin levels. This interference in immunoassays necessitates careful interpretation of drug concentrations and clinical correlation.
Area of Science:
- Clinical Chemistry
- Immunochemistry
- Laboratory Medicine
Background:
- Vancomycin and digoxin require therapeutic drug monitoring due to potential toxicity.
- Paraprotein interference with vancomycin assays is known, but not with digoxin assays.
Observation:
- A patient on vancomycin and digoxin showed persistently low serum concentrations by Abbott PETINIA method.
- Alternative methods revealed toxic drug levels, prompting drug cessation.
Findings:
- Free kappa light chains, potentially in polymeric form, are suspected to cause falsely low vancomycin and digoxin levels.
- Turbidity and agglutination in patient samples suggest assay interference.
- Protein-free filtration partially corrected the drug measurements.
Implications:
- Clinicians and pharmacists must consider assay interference when drug levels conflict with clinical presentation.
- Laboratory investigation for interfering substances is crucial for accurate therapeutic drug monitoring.
- This case highlights a novel interference mechanism in particle-enhanced turbidimetric immunoassay methods.
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