Setting system suitability criteria for detectability in high-performance liquid chromatography methods using signal-to-noise ratio statistical tolerance intervals

For pharmaceutical products, one approach developed to assure that different chromatographic systems are capable of generating valid results is the system suitability test. Typically, a system suitability test involves numerical limits for predefined chromatographic parameters such as theoretical plates, tailing factor, injector reproducibility, etc. An estimation of the ratio of signal compared to baseline is one way to measure system performance, according to a valid method, independent of the instrument. However, since this comparison relates the height of the signal to the height of the noise, it is difficult to relate to the peak area measurements that are typically used for quantification of samples. Additionally, although peak area and peak height may be highly correlated over a wide region, peak area at very low concentrations can be more sensitive to all components of noise due to peak shape. To establish a system suitability criterion, one can use the ratio of the area signal to the baseline noise for replicate injections for samples prepared at concentration equal to the limit of quantitation during the validation studies. A lower limit for this ratio can be derived using statistical tolerance intervals. This lower limit can be applied as a system suitability criterion to measure that any system is performing adequately for measuring low level components in the sample for all future use of the method. (C) 2001 Elsevier Science B.V. All rights reserved.