Development of Stereoselective Method for the Quantification of Stereoisomers and Geometrical Isomer of Pitavastatin Calcium by Enhanced Approach

A new, simple, selective, and robust normal-phase method for the accurate quantification of all the four stereoisomers and one geometrical isomer of pitavastatin calcium (PIT) in drug substances and drug products was developed. The method is capable of quantifying all the isomers in the presence of other related substances. Separation was achieved using immobilized amylose stationary phase (Chiralpak IA) with a mixture of n-heptane, 1-butanol, methanol, formic acid, and diethylamine. Multivariate analysis and statistical tools were used to develop this highly robust method in a short span of time. A central composite design was employed to study the main effects and interactions of the independent variables. The method exhibited consistent, high-quality recoveries [97.3 ± 1.7 to 99.3 ± 2.1 (mean ± RSD)] with a high precision for all the isomers. Linear regression analysis revealed an excellent correlation between peak responses and concentrations (r ² values of 0.9990–0.9998) for the isomers. The method is sensitive enough to quantify any isomers above 0.02 % and detect any isomer above 0.006 % in PIT. Forced degradation studies proved that the method is specific for isomers. m/z values were determined for the major degradants and their possible structures were proposed on the basis of the known reactivity.     

Unexpected Synthesis of Highly Substituted Indole Derivatives

An unexpected synthesis of highly substituted indole derivatives was provided by treating 2-[2-(4-fluorophenyl)-2-oxo-1-phenylethyl]-4-methyl-3-oxo-pentanoic acid phenylamide with aryl hydrazines in the presence of trifluoroacetic acid in tetrahydrofuran.     

Ultra-High Performance Method on Superficially Porous Stationary Phase for the Determination of Related Substances in Pitavastatin Calcium by HPLC

A simple reverse-phase method for the selective quantification of pitavastatin calcium (PIT) and its related substances was developed. The method demonstrated an excellent separation between PIT and each of 15 impurities (including its isomers and degradants) within a short run time of 12 min by HPLC. A rapid resolution similar to that of UHPLC was achieved using high flow rate on superficially porous C18 stationary phase. A synergistic combination of quality by design approach and use of a superficially porous column delivered a HPLC method with ultra-high performance. Forced degradation studies proved the method to be highly specific (mass balance > 98 %) and the structures of major degradation products were proposed based on LC–MS analysis. The results of validation proved the method to be highly precise (%RSD < 4), accurate (recoveries in range of 100 ± 7 %), linear (r ² > 0.999) and sensitive (LOQ ≤ 0.02 % and LOD ≤ 0.005 %) for all the impurities and drug. Use of multivariate analysis helped to incorporate high robustness in the method. The method is valuable for quantification of PIT and its related substances in both drug substance and oral solid dosage form.

     

Cystoseira algae (Fucaceae): update on their chemical entities and biological activities

Cystoseira (Sargassaceae) is a genus of marine brown algae composed of about 40 species, which is distributed along the Eastern Atlantic and Mediterranean coasts. The biological potential of the Cystoseira genus has been investigated and several activities have been reported. Chemically, this genus contains a wide variety of secondary metabolites, such as terpenoids, steroids, phlorotannins and phenolic compounds. Additionally, other chemical components as, for instance, carbohydrates, triacylglycerols/fatty acids, pigments as well as vitamins have been identified in the studied species. Some of the isolated compounds were associated with the reported pharmacological properties, as for example antioxidant, anti-inflammatory, cytotoxicity, anticancer, cholinesterase inhibition, anti-diabetic, activities but also antibacterial, antifungal and anti-parasitic activities. In this review, we provide a comprehensive overview of the compounds isolated and identified after 1995 from the different species of Cystoseira, compiling more than 200 compounds isolated, together with their therapeutic potential.