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 β-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.
Measurement uncertainty, no doubt, is an important element in examining and interpreting the results obtained in chemical analyses, particularly in the pharmaceutical field. Obviously, this is required by several guides and standards; however, few documents are interested in estimating the measurement uncertainty associated with dissolution test results. In this paper, the Guide to the expression of Uncertainty in Measurement (GUM) and its Supplement 1 "Monte-Carlo Simulation" (MCS) were used, side by side, to estimate the measurement uncertainty of two dissolution test methods, each using a different instrumental technique, namely UV-Visible Spectrophotometry and High Performance Liquid Chromatography (HPLC). A comparative study of both approaches was successfully conducted then with the aim of not only examining the compatibility between the results of the two methods, but also the presentation and discussion of the advantages and limitations of the applicability of each approach in drug analyses. The results obtained with the ISO-GUM and the Monte-Carlo simulation, for the two cases of analysis, revealed comparability between the estimates of uncertainty. Indeed, the standard uncertainties obtained by the two approaches are very close (uGUM Repaglinide (RG) = 1.1885% & uMCM Repaglinide (RG) = 1.1854% and uGUM Irbesartan (IB) = 1.4028 % & uMCM Irbesartan (IB) = 1.3071%). On the other hand, it has been found that the ISO-GUM approach slightly overestimates the expanded uncertainty because of the used value k = 2 of the coverage factor. Moreover, we have found that the conditions of applicability of the analytical approach and its numerical complement are not always obvious, in particular, when the model of calculation of the measurand is complicated and the instruments of measurements used are complex.
The present work aims at elucidating the changes in the chemical composition of Moroccan cedar wood during exposure time to the natural degradation process. Correlation of these changes with certain physical properties and performance of this polymeric material were proposed. Four archaeological Cedrus atlantica wood samples dating from the 16th, 17th, 19th and 21st centuries were analyzed using Fourier Transform Infrared spectroscopy. The infrared spectroscopic analyses demonstrated in detail the significant changes that occurred in different molecular groups of lignocelluloses fibers, as evidenced by the decrease of band intensities related to the carbohydrates and lignin. The influence of the natural degradation process on these fibers was enhanced by the gradual decline in fingerprint (1800-800cm-1) related to the cellulose amount accompanied by the detection of new carbonyl band at 1650cm-1 attributed to the C=O quinone suggesting the lignin’s oxidation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.