title: Therapeutic Drug Monitoring of Lithium: A Study of the Accuracy and Analytical Variation Between Laboratories in Denmark.
abstract: BACKGROUND
  Serum lithium is monitored to ensure levels within the narrow therapeutic window. This study examines the interlaboratory variation and inaccuracy of lithium monitoring in Denmark.
  
  
  METHODS
  In 16 samples consisting of (1) control materials (n = 4), (2) pooled patient serum (n = 5), and (3) serum from individual patients (n = 7), lithium was measured in 19 laboratories using 20 different instruments. The lithium concentrations were targeted by a reference laboratory. Ion-selective electrode (n = 5), reflective spectrophotometric (RSM, n = 5), and spectrophotometric (n = 10) methods were used.
  
  
  RESULTS
  Acceptable accuracy-interpreted as total differences from target values (bias) less than or equal to ±12%-was generally found in patient samples above 0.7 mmol/L. Below 0.7 mmol/L, 8 instruments had 2 or more patient samples exceeding a difference to the targeted reference value of >12%. Seven of these instruments had a systematic positive or negative bias and more so at lower lithium concentrations. Three poorly calibrated instruments were found in the ion-selective electrode group, 3 in the spectrophotometric group, and 2 in the RSM group. The instruments using reflectance spectrophotometry (RSM) were on average 21% positively biased when measuring control materials. However, this effect was not observed in patient samples.
  
  
  CONCLUSIONS
  Large interlaboratory variation was found below 0.7 mmol/L because of 7 instruments with a poor accuracy and 1 with poor precision. Methods should be recalibrated or substituted. Controls below 0.7 mmol/L are recommended.
authors.affiliation: *Department of Clinical Biochemistry, OUH, Svendborg Hospital; †Department of Clinical Chemistry and Pharmacology, Odense University Hospital; and ‡Department of Psychiatry, Svendborg Hospital, Denmark.
authors.forename: Tina
authors.initials: T
authors.lastname: Mose
authors.forename: Per
authors.initials: P
authors.lastname: Damkier
authors.forename: Magnus
authors.initials: M
authors.lastname: Petersen
authors.forename: Steen
authors.initials: S
authors.lastname: Antonsen
mesh_terms: D003718:Denmark; D016903:Drug Monitoring / Q000592:standards* / Q000706:statistics & numerical data*; D006801:Humans; D017736:Ion-Selective Electrodes; D059021:Laboratory Proficiency Testing / Q000592:standards* / Q000706:statistics & numerical data*; D008094:Lithium / Q000097:blood*; D012016:Reference Values; D013053:Spectrophotometry
chemical_list: D008094:Lithium