Evaluating Patient Medians for Laboratory Quality Control Using Long-Term Carbamazepine Monitoring Data

Carbamazepine is an antiepileptic and mood-stabilizing drug with complex pharmacokinetics and a narrow therapeutic index, making therapeutic drug monitoring (TDM) essential. The therapeutic reference range for carbamazepine at our laboratory is 20-40 µmol/L (4.7-9.4 mg/L). Long-term laboratory data may help identify population trends, seasonal or demographic variation, and the suitability of patient-derived medians as a quality-assurance tool.

This retrospective study analyzed 12 577 serum carbamazepine results obtained between May 2007 and December 2025 at Uppsala University Hospital. The total number of unique individuals providing the test results was 3147. Demographic variables (age, sex) and sampling dates were included. Yearly percentiles were used to evaluate long-term trends, and monthly variation was assessed for seasonal effects. Equivalence of analytical results was examined during the transition from the Architect ci8200 to the Cobas Pro c503 platform (February 2021).

Annual test volume peaked in 2010 (n = 955) and declined to 160 by 2025. Despite reduced testing, carbamazepine concentrations increased steadily over time, with median values rising from 25.2 µmol/L (5.9 mg/L) in 2007 to 31.2 µmol/L (7.4 mg/L) in 2025. Seasonal analysis showed predictable drops in sampling during the Swedish summer vacation period but no meaningful variation in drug concentrations. The method transition in February 2021 showed strong agreement between platforms, with slightly higher values on the Cobas system (Cobas = 1.049 × Architect - 0.164; R2 = 0.946).

Carbamazepine concentrations in routine patient samples have gradually increased over 2 decades, independent of declining test frequency. Seasonal workload fluctuations did not affect observed levels. Patient-derived medians were stable and sensitive to method changes, supporting their role as complementary internal quality-control tools. Long-term TDM databases provide valuable insights for both clinical interpretation and laboratory quality assurance.