Accuracy and precision of gas-liquid chromatographic, high-pressure liquid chromatographic, and enzyme immunoassay techniques for the measurement of theophylline concentrations in serum: a comparison based on external quality assurance measurements.

The accuracy and precision of gas-liquid chromatography with and without derivatization (GLC + D, GLC-ND), high-pressure liquid chromatography (HPLC), and enzyme multiplied immunoassay (EMIT) for the measurement of serum levels of theophylline were compared below, within, and above the therapeutic range (55-110 mumol/L) using data from 63 samples from the Heathcontrol quality assurance scheme. Within the therapeutic range, the methods did not differ in either precision or accuracy. Coefficients of variation (CV) of measurements were between 12 and 16%, and measurements did not differ from spiked values. Below the therapeutic range, the methods differed significantly. The GLC methods had the lowest precision (CV 23-25%), while the CV for HPLC was 19% and for EMIT 14%. GLC + D and HPLC also overestimated drug level by 11 and 8%, respectively. Above the therapeutic range, the precision of the methods did not differ (CV 10-13%), although both EMIT and HPLC underestimated theophylline level by 5-6%. In a comparison of individual laboratories based on a ranking of overall precision, laboratories employing GLC commonly exhibited less precise rank positions than laboratories using EMIT. Laboratories making HPLC measurements showed a bimodal distribution but no methodological differences were identified to explain this difference in precision.