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Background Hypertension is a critical health problem; it is a prevalent risk factor for cardiovascular disease. Many treatments to combat hypertension are available, while several patients are resistant to the standard therapeutic approaches. The association of two or more substances in a fixed-dose combination is effective and tolerated to substitute the standard therapeutic approach. Objective New UPLC-DAD method was developed and validated to assay a combination of eight antihypertensive drugs including a diuretic: hydrochlorothiazide, dihydropyridine calcium channel blocker: Amlodipine and angiotensin II type 1 receptor blockers (sartans): valsartan, candesartan, eprosartan, olmesartan, losartan, and irbesartan in the pharmaceutical matrix. Methods Chromatographic separation was performed on an Acquity® UPLC C18 1.7 µm 2.1 × 100 mm column, with a gradient of buffer solution and acetonitrile, in the proportion of (80:20 v/v). Results Good resolution was obtained, and an optimal analysis time of less than 5 min was achieved. The method was validated according to the International Conference on Harmonization (ICH) guidelines following the classical approach and accuracy profile, it is shown to be suitable for intended applications. The method was successfully used for quality control laboratories and the determination of these drugs combination in pharmaceutical dosage forms.

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.

Background Levofloxacin is a third-generation fluoroquinolone that has several advantages over its R-Ofloxacin isomer. It is used to treat different types of infections including urinary and prostatitis. Objective New HPLC method for the enantioselective separation of levofloxacin and its chiral impurity was developed and validated to improve the separation of the enantiomers of levofloxacin (impurity-R and active principle-S) by increasing the value of the resolution between the eutomer and the distomer. Methods Chromatographic separation was performed on Prodigy ODS -2, 5 µm 4.6 × 150 mm column, with a gradient of buffer solution and methanol, in the proportion of (80:20, v/v). The box-Behnken design was considered when optimizing the enantioseparation involving many factors effects such as the concentration of D-phenylalanine, the pH of the buffer, the percentage of organic modifier in the mobile phase, the flow rate, the temperature of the column, and the type column. Results Chiral separation was achieved with an optimal resolution of 3.8. The method was successfully validated following ICH Q2 (R1) guideline, fulfilling acceptance criteria for selectivity (no interference in the retention time of S-levofloxacin and R-levofloxacin), linearity [r > 0.999 in the ranges 1.25 to 3.75 µg/mL for all enantiomers], and precision (RSD < 2%). Accuracy was assessed by the application of the analytical method to an analyte of know purity, evidencing the usefulness of this monitoring system. Conclusions The method was successfully used for the determination of levofloxacin impurity in raw material and pharmaceutical dosage forms.