Guidance for robustness/ruggedness tests in method validation

Heyden, Yvan Vander; Nijhuis, Arend; Smeyers‐Verbeke, J.; Vandeginste, B.G.M.; Massart, D.L.

doi:10.1016/s0731-7085(00)00529-x

Cited by 541 publications

(308 citation statements)

References 19 publications

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“…The robustness of the method was evaluated to establish the capability of the method by changing the experimental conditions and studying its impact on the system suitability 22 . Robustness was performed by changing the method parameters like mobile phase flow rate and column temperature.…”

Section: Robustnessmentioning

confidence: 99%

Untitled

2017

IJPSR

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A simple, sensitive and stability indicating reverse phase high performance liquid chromatography method (RP-HPLC) was developed and validated for the estimation of Lapatinib and its related substances in bulk and finished dosage forms. The newly developed method was assessed using Zorbax Eclipse C18 (3.5 µm, 100 × 4.6 mm) HPLC column with pH-4.5 ammonium formate buffer and acetonitrile as mobile phase in gradient elution mode with a run time of 35 minutes. UV detection was carried out at a wavelength of 261 nm with an injection volume of 5 µL. The developed method was validated as per the ICH guidelines with respect to precision, accuracy, linearity, robustness, specificity and system suitability. Lapatinib samples were exposed to thermal, photolytic, acidic, basic and oxidative stress conditions. The stressed samples were analyzed by the developed method to establish the stability indicating power of the method. The LOD values were 0.009, 0.012 and 0.011 µg/ml and the LOQ values were 0.027, 0.035 and 0.0304 µg/ml respectively for impurity-1, impurity-2 and impurity-3 of Lapatinib. The average recovery values of Lapatinib related substances were found to be in the range of 97.5-101.2 %. The developed method was linear over a range of 0.027-1.5 µg/ml for Lapatinib impurities. The proposed method was found to be suitable and accurate for the determination of Lapatinib related substances in bulk and finished formulations.

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Section: Robustnessmentioning

confidence: 99%

Untitled

2017

IJPSR

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“…The robustness of an analytical method is a measure of its capacity to remain unaffected by small, but deliberate variations in method parameters and provides an indication of its reliability during normal usage [26,27]. Robustness testing is nowadays well known and widely applied, especially in the pharmaceutical industries that must comply with strict regulations.…”

Section: Fig 1 Chemical Structures Of Hydrochlorothiazide and Valsamentioning

confidence: 99%

“…The graphical interpretation may be based on a halfnormal probability plot, while the statistical interpretation on the approach of Dong [27]. In this approach, an initial estimate of error on an effect, S 0 , is obtained with the following equation.…”

Section: Robustness Studiesmentioning

confidence: 99%

Total error-based validation including the experimental design-based robustness evaluation of a stability-indicating method for the simultaneous quantification of hydrochlorothiazide and valsartan in tablet formulations

Elkarbane¹,

AL-Kamarany²,

Bouchafra

et al. 2015

Acta Chromatographica

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Summary.A gradient reversed phase high-performance liquid chromatography (RP-HPLC) method with ultraviolet (UV) detection to analyze hydrochlorothiazide (HCT) and valsartan (VS) simultaneously in a tablet formulation during forced degradation studies was developed. This method was validated using a novel approach, namely, the accuracy profile or total errors approach. The robustness of the method was evaluated using a Plackett-Burman design for eight factors. The algorithm of Dong was applied to determine the significant factor effects. The validation results showed that the method is precise (RSD: 1.14% for HCT and 0.43% for VS) and accurate (mean recovery: 99.90% for HCT and 99.98% for VS). On the other hand, the results of the robustness study showed that the type of column was the important factor which affects a number of responses, namely, the asymmetry factor (AF), retention time (RT), and resolution (RS). However, the assay results were not affected; therefore, the method can be considered robust. Finally, the method was applied to study the stability of HCT and VS under forced conditions. Significant results were obtained with basic hydrolysis, oxidation, and thermal stress, while the accelerated and acidic conditions did not affect the stability of HCT or VS.

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“…The experiments to study the influence of these small changes are usually evaluated more 53 efficiently by means of experimental design approaches with the factors at two levels, mostly 54 by using screening designs, either a saturated fractional factorial or a Plackett-Burman design 55 [6,7,8,9,10]. 56 57…”

Section: /24 43mentioning

confidence: 99%

“…In this situation, a standard design, such as a Plackett-Burman [6] estimates of the coefficients related to blocks and of the remaining coefficients should be 178 null, or at least, the closer to zero the better. This is so in order to guarantee that the 179 interpretation of the effects of the experimental factors is independent of the block effect.…”

Section: Construction Of the Experimental Design 127 128mentioning

confidence: 99%