Validation of an HPLC Method for the Determination of Diclofenac Diethylamine and Three of Its Impurities in a Gel Pharmaceutical Form.

BACKGROUND: Monitoring impurities in drug products is a principal requirement of pharmaceutical regulatory authorities all over the world to ensure drug safety. For this reason, there is a great need for analytical QC of dugs products. OBJECTIVE: In this study, a simple, efficient, and direct HPLC method was developed for the determination of three impurities of diclofenac. METHODS: The HPLC method was developed using a mobile phase which consisted of an HPLC grade mixture, acetonitrile-0.01M phosphoric acid adjusted to pH 2.3 (1 + 3, by volume). RESULTS: The separation was performed in 15 min. The calibration curves of the three impurities were linear; the correlation coefficients were 0.999 at concentrations of 0.00015-0.003 µg/mL. CONCLUSION: The validation of this method shows that it meets all validation criteria. This shows the reliability of this method for the routine control of diclofenac impurities. HIGHLIGHTS: The validation of a robust HPLC method for the determination of diclofenac impurities is of great importance for the pharmaceutical industry to control its products.

GAMOS/GEANT4 simulation and comparison study of X-ray narrow-spectrum series at the national Secondary Standard Dosimetry Laboratory of Morocco.

This study aimed to simulate the X-ray Irradiator narrow-spectrum series and compare the results with experimental and recommended values in ISO standards. X-Ray beam qualities of N-40 to N-300 were established experimentally at the national Secondary Standard Dosimetry Laboratory (SSDL) of Morocco in purpose of calibrating radiation protection- level. The variations between the first half-value layer (1st HVL) and the second (2nd HVL) for experimental were within 5%. Also, homogeneity coefficients h were mostly between 0.75 and 1 according to ISO. GAMOS Monte Carlo code was used to simulate the radiation quality of narrow-spectrum series between N-40 to N-150. All 1st HVL, 2nd HVL, and h simulation values were compare with experimental and ISO values. In MC codes and GAMOS, there is no direct way to generate the X-ray spectrum if we do not have details of the X-ray tube geometry, dimensions and materials. Therefore, Institute of Physics and Engineering in Medicine report number 78 was used to generate the X-ray spectrums in purpose to test this method accuracy. The simulation results for the 1st HVL and 2nd HVL showed a good agreement with experimental data and with ISO 4037-1:1996 given values. Also, the comparison results showed that most of the homogeneity coefficients are within the ISO standard range.

Optimization of a Ligand Exchange Chromatography Method for the Enantioselective Separation of Levofloxacin and Its Chiral Impurity.

BACKGROUND: Levofloxacin is a third-generation fluoroquinolone that has several advantages over its (R) ofloxacin isomer. It is used to treat different types of infection, including urinary infection and prostatitis. OBJECTIVE: A 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. METHOD: Chromatographic separation was performed on a Prodigy ODS -2, 5 µm 4.6 × 150 mm column, with a gradient of buffer solution and methanol (80:20, v/v). A Box-Behnken design was considered when optimizing the enantioseparation involving the effects of many factors 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 of column. RESULTS: Chiral separation was achieved with an optimal resolution of 3.8. The method was successfully validated following the International Conference on Harmonization Q2 (R1) guideline, fulfilling the acceptance criteria for selectivity [no interference in the retention time of (S) levofloxacin and (R) levofloxacin], linearity (r ≥0.999 in the range 1.25-3.75 µg/mL for all enantiomers), and precision (RSD <2%). Accuracy was assessed by the application of the analytical method to an analyte of known purity, providing evidence for 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. HIGHLIGHTS: The following method is accurate and robust to quantify and characterize the presence of levofloxacin impurity in raw material for pharmaceutical compounds.

Development and Validation of a UPLC-DAD Method for the Simultaneous Quantification of Eight Antihypertensive Drugs in the Pharmaceutical Matrix.

BACKGROUND: Hypertension is a critical health problem; it is a prevalent risk factor for cardiovascular disease. Many treatments to combat hypertension are available, however many patients are resistant to the standard therapeutic approaches. The association of two or more substances in a fixed-dose combination is effective and tolerated as a substitute for the standard therapeutic approach. OBJECTIVE: The new ultra performance liquide chromatography 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 guidelines following the classical approach and accuracy profile, and it is shown to be suitable for intended applications. The method was successfully used for quality control laboratories and the determination of these drugs combinations in pharmaceutical dosage forms.

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.

2-Phenyl-thieno[2,3-b]quinoxaline.

The title compound, C(16)H(10)N(2)S, is almost planar (r.m.s. deviation for all non-H atoms = 0.080 Å). The dihedral angle between the three fused-ring system and the phenyl ring is 9.26 (3)°. The S atom and the opposite C atom of the thio-phene ring are mutually disordered with an occupancy ratio of 0.7706 (19):0.2294 (19).