Proficiency-testing issues relating to sirolimus.
BACKGROUND
A need exists to document laboratory proficiency to (1) compare results produced by different analytical techniques and (2) ensure consistency of results from multiple testing sites.


OBJECTIVE
To enable concentration-controlled studies of sirolimus to proceed with confidence, proficiency-testing schemes were put in place at laboratories selected to act as reference laboratories. The feasibility of establishing an ongoing proficiency-testing scheme was addressed with respect to sample stability. The scheme was then used to test proficiency for the measurement of sirolimus in 3 blinded samples each month.


METHODS
The method chosen for measurement of sirolimus was a prototype microparticle enzyme immunoassay. Initially, 15 laboratories were asked to analyze a series of 85 blinded samples that tested their inaccuracy, repeatability, and reproducibility for the measurement and their ability to dilute over-range samples competently. Both blood samples spiked with sirolimus and pooled blood samples from patients receiving the drug were circulated to a maximum of 50 laboratories.


RESULTS
Overall, both inaccuracy and imprecision were acceptable by predefined criteria. Inaccuracy for the immunoassay (percentage difference of the measured value against the nominal value) averaged -5% (95% CI, -9% to -1%). The mean percentage difference between the immunoassay and a high-performance liquid chromatographic assay with mass-spectrometric detection for the measurement of sirolimus in pooled samples (n = 5) from patients receiving the drug was 29% (95% CI, 24% to 34%).


CONCLUSIONS
The techniques documented here as part of the International Sirolimus Proficiency Testing Scheme could be applied to other clinical studies requiring protocol-driven dosing adjustments based on sirolimus measurements, irrespective of analytical technique used.
Jones
K
K
Analytical Unit, St. George's Hospital Medical School, London, England.
Johnston
A
A
Holt
D W
DW
D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007118:Immunoassay; D007166:Immunosuppressive Agents / Q000097:blood*; D007753:Laboratories / Q000592:standards*; D010865:Pilot Projects; D011933:Reagent Kits, Diagnostic; D015203:Reproducibility of Results; D020123:Sirolimus / Q000097:blood*; D013056:Spectrophotometry, Ultraviolet; D013997:Time Factors
D007166:Immunosuppressive Agents; D011933:Reagent Kits, Diagnostic; D020123:Sirolimus