Assessment of liquid chromatographic method robustness by use of Plackett-Burman design

Abstract

Robustness testing is an important part of method validation. Many ideas on robustness testing can be found in the literature, but the most useful approach is application of experimental design. In the work discussed in this paper, Plackett-Burman design was used for robustness testing of an LC method. Robustness was assessed for a previously validated method developed for chromatographic analysis of perindopril tert-butylamine and its impurities. Eleven factors (seven real and four dummies) in twelve experiments were examined. Robustness was assessed by graphical (half-normal probability plots and Pareto charts) and statistical (t-test) methods. For estimation of the standard error of effect (necessary for t-test estimation) calculations based on negligible effects and Dong's algorithm were used at the significance levels α = 0.05 and α = 0.01.In this way the effect of the factors was completely defined and, furthermore, nonsignificant intervals for significant variables were calculated. Finally, on the basis of the worst-case situation, system-suitability tests were performed and acceptance limits for certain values were calculated.

Systematical approach in evaluation of LC method for determination of raloxifene hydrochloride and its impurities employing experimental design

“…In the next step, the method’s robustness evaluation was done using Plackett–Burman design. Theory of Plackett–Burman design is given by Vander Heyden et al [4] and we have already used this design for robustness testing in the method validation [5] , [24] . So, in this paper only data important for the analyzed case are given.…”

Avoiding the False Negative Results in LC Method Robustness Testing by Modifications of the Algorithm of Dong and Dummy Factor Effects Approach

“…The experiments defined by Plackett-Burman design allow effects of the selected factor to be calculated [2,[13][14][15] as:…”

Plackett-Burman design in robustness testing of liquid chromatographic method for determination of sodium-valproat

“…skrining vrsta dizajna. U literaturi se može naći primena Plaket-Burman dizajna [9][10][11], kao i punog faktorskog [12][13][14][15][16] i frakcionog faktorskog dizajna [17][18][19][20][21]. S obzirom da je u ovom radu primenjen Plaket-Burman dizajn, onda će on ovde i biti detaljnije opisan.…”