Intra-GUM comparisons for the estimation of measurement uncertainty: Application to a chromatographic assay of four statins in a dry form.

The chromatographic method (HPLC) is well-known for its dependability and precision in pharmaceutical analyses for assessing the quality and efficacy of drug products. However, the characteristics of the HPLC method make sense only after a careful evaluation of the measurement uncertainty. Nevertheless, it has been observed that precise identification of the sources of uncertainty resulting from the operational mode using the HPLC technique to assess their standard uncertainty based on the ISO-GUM approach is not obvious. Because of our extensive bibliographic search, we noticed that many studies published on the estimate of the uncertainty in chromatographic methods (HPLC) using the Eurachem/Citac guide are somewhat diverse in their use of this approach. The documentary research revealed four mathematical models namely, GUM1, GUM2, GUM3, and GUM4 that are most used to estimate the measurement uncertainty of the HPLC technique. Hence, a comparison between the four GUM mathematical models was carried out graphically and statistically using one-way ANOVA followed by Tuckey and Scheffe tests. The comparison results show a significant difference, which may create confusion in the reporting of measurement results as well as problems in making sound decisions. This leads to the suggestion that alternative approaches, such as the approach of a total error or ISO 11325, be used to check the ISO-GUM method's calculations of measurement uncertainty.

Application of Design Space, Uncertainty, and Risk Profile Strategies to the Development and Validation of UPLC Method for the Characterization of Four Authorized Phosphodiesterase Type 5 Inhibitors to Combat Counterfeit Drugs.

BACKGROUND: Counterfeit medicines are an increasing scourge that are difficult to identify and they have become industrialized and widespread through highly organized illegal channels. OBJECTIVE: This research aims to develop a robust method to determine four phosphodiesterase type-5 inhibitors in counterfeit drugs based on ultra-performance liquid chromatography. METHOD: Experimental design methodology (DOE) and design space (DS) recommended by ICH Q8 were used side-by-side in the development phase to define the optimal parameters as well as the robustness of the chromatographic method. Moreover, both the uncertainty and risk profile derived from the ß-content and γ-confidence tolerance interval were investigated during the validation phase to examine the performance of this method. RESULTS: Successful chromatographic results, in a high resolution between the four active ingredients and an optimal analysis time of less than 1.6 min, were achieved at the end of the optimization phase. In addition, validation results show a low risk of future measurements outside acceptance limits set at 5%. CONCLUSIONS: Our procedure was successfully applied in the routine phase to identify 23 illicit formulations of an erectile dysfunction drug. HIGHLIGHTS: An efficient method for the characterization of 4 authorized phosphodiesterase in less than 1.6 min was established. A DS approach was applied to test the performance of this analytical method during analytical development. A risk profile was then carried out to approve the validity of the analytical method through the uncertainty profile approach.