Theoretical repeatability assessment without repetitive measurements in gradient high-performance liquid chromatography

• ISO 11843-7 was applied to repeatability estimation in gradient HPLC with UV detection (HPLC-UV).
• A long-term baseline, if a drift is eliminated, is regarded by stochastic processes.
• The RSDs of measurements were obtained by the stochastic treatment of the baseline noise.
• The presented estimation was applied to the evaluation of “system repeatability”.
• The theoretical SD estimate is as stochastically reliable as the statistical SD estimate (n = 31).

This paper puts forward a time and material-saving method for evaluating the repeatability of area measurements in gradient HPLC with UV detection (HPLC-UV), based on the function of mutual information (FUMI) theory which can theoretically provide the measurement standard deviation (SD) and detection limits through the stochastic properties of baseline noise with no recourse to repetitive measurements of real samples. The chromatographic determination of terbinafine hydrochloride and enalapril maleate is taken as an example. The best choice of the number of noise data points, inevitable for the theoretical evaluation, is shown to be 512 data points (10.24 s at 50 point/s sampling rate of an A/D converter). Coupled with the relative SD (RSD) of sample injection variability in the instrument used, the theoretical evaluation is proved to give identical values of area measurement RSDs to those estimated by the usual repetitive method (n = 6) over a wide concentration range of the analytes within the 95% confidence intervals of the latter RSD. The FUMI theory is not a statistical one, but the “statistical” reliability of its SD estimates (n = 1) is observed to be as high as that attained by thirty-one measurements of the same samples (n = 31).