New enantioselective liquid chromatography method development and validation of dipeptidyl peptidase IV inhibitors using a macrocyclic glycopeptide (vancomycin) chiral stationary phase under polar ionic mode condition.

The direct separation of dipeptidyl peptidase IV (DPP-4) inhibitors such as Sitagliptin (STG), Linagliptin (LIG), and Saxagliptin (SAG) enantiomers in normal phase conditions have been achieved on immobilized polysaccharide-based chiral stationary phases (CSPs), as well as on the macrocyclic glycopeptide vancomycin chiral stationary phase (Chirobiotic V2) under polar ionic mode. The enantiomers of these targets could be separated completely (resolution factor Rs > 2) using the Chirobiotic V2 column in polar ionic mode with the mobile phase (MeOH/AcOH/TEA 100/0.3/0.1 v/v/v) in an isocratic elution at 1.0 ml min-1 . The effect of the mobile phase composition on separation, including buffer salts, acid-base modifiers, and analyte structures, was evaluated. The developed technique was validated in the polar ionic mode according to the International Conference on Harmonization (ICH) Q2R1 guidelines in terms of accuracy, precision, selectivity, linearity, limit of detection (LOD), and limit of quantification (LOQ). The calibration curve was linear in a concentration range from LOQ to 3.75 µg/ml. The LOD and LOQ of STG, LIG, and SAG were 0.15 and 0.45, 0.15 and 0.50, 0.16 and 0.50, respectively. The proposed method is said to be selective, accurate, and precise. Finally, the validated method was used successfully for the quantitative determination of DPP-4 enantiomers in pharmaceutical analytes.

Synthesis of 2-aryl-5-(arylsulfonyl)-1,3,4-oxadiazoles as potent antibacterial and antioxidant agents.

Ten novel 2-aryl-5-(arylsulfonyl)-1,3,4-oxadiazoles were produced and assessed for their in vitro antibacterial and antioxidant activities. Diverse spectroscopic methods like 1H NMR, 13C NMR, IR, and LCMS were used for the characterization of the prepared samples and all the data was in good agreement with the anticipated structures. The prepared compounds 6a-j were screened for their in vitro antibacterial activity against bacterial strains Pseudomonas aeruginosa, Enterobacter aerogenes, Escherichia coli (gram-positive), and Bacillus cerus, Staphylococcus aureus, Bacillus subtilis (gram-negative). The antimicrobial screening outcome revealed that the prepared 2-(3,4-dimethylphenyl)-5-tosyl-1,3,4-oxadiazole (6j), 2-(3-isopropylphenyl)-5-tosyl-1,3,4-oxadiazole (6c), and 2-(2-ethylphenyl)-5-tosyl-1,3,4-oxadiazole (6i) are most potent among all the examined compounds. Furthermore, the antioxidant activity of the prepared compounds was also investigated by DPPH radical scavenging method and the results showed that some of the compounds were moderately active.

Copper-Promoted One-Pot Approach: Synthesis of Benzimidazoles.

A facile, one-pot, and proficient method was developed for the production of various 2-arylaminobenzimidazoles. This methodology is based for the first time on a copper catalyst promoted domino C-N cross-coupling reaction for the generation of 2-arylaminobenzimidazoles. Mechanistic investigations revealed that the synthetic pathway involves a copper-based desulphurization/nucleophilic substitution and a subsequent domino intra and intermolecular C-N cross-coupling reactions. Some of the issues typically encountered during the synthesis of 2-arylaminobezimidazoles, including the use of expensive catalytic systems and the low reactivity of bromo precursors, were addressed using this newly developed copper-catalyzed method. The reaction procedure is simple, generally with excellent substrate tolerance, and provides good to high yields of the desired products.

Copper-catalyzed synthesis of 2-aminophenyl benzothiazoles: a novel approach.

A novel, convenient and efficient protocol for the construction of various 2-aminophenyl benzothiazoles by domino intra- and intermolecular C-N cross-coupling reactions of arylisothioureas with aryl iodides using an inexpensive, air stable and readily available copper catalyst is described. The arylisothioureas were obtained from thiourea via copper promoted desulfurization followed by nucleophilic substitution. In addition, the reactivity of arylhalides and the reaction mechanism have also been studied. The protocol features operational simplicity and a broad substrate scope.

Physiochemical properties of aminophylline-dextrose injection admixtures.

The compatibility and stability of aminophylline-dextrose injection admixtures were investigated. Aliquots of 5% dextrose injection, 0.9% sodium chloride injection, and 5% dextrose and 0.9% sodium chloride injection were studied for these physiochemical properties: pH, color, clarity, absorbance in a spectrophotometer at 400 nm, and hydroxymethylfurfural (HMF) content. Aminophylline injection was added to the solutions, and aliquots were withdrawn after 0, 6, 24, and 48 hours of storage at 5, 25, 35, and 55 degrees C for testing of the physiochemical properties and aminophylline content. An aminophylline admixture in 5% dextrose injection was passed through an in-line filter (IVEX-2), and eluents were collected for aminophylline assay and for testing the above physiochemical properties. HMF and theophylline were assayed to high-pressure liquid chromatography (HPLC). The aminophylline concentration remained constant in all admixtures studied. A yellow color developed in dextrose-containing aminophylline admixtures stored at 25, 35, and 55 degrees C for 48, 24, and 6 hours, respectively. HMF concentration, pH, and clarity remained within compendial limits. The in-line filter did not retain active ingredients or alter the physiochemical properties of the admixture. Solutions that were yellow showed additional peaks on HPLC. HMF seemed to be a precursor for this yellow color, inasmuch as HMF concentration increased with increasing color intensity. It is concluded that aminophylline-dextrose admixtures are visually and chemically stable for 48 hours when stored under refrigeration or at room temperature.

Intravenous solution compatibility and filter-retention characteristics of trace-element preparations.

The compatibility of recently published AMA formulations of the four trace-element injections (zinc, copper, chromium, and manganese) with a representative total parenteral nutrition (TPN) formulation and commonly used intravenous solutions was evaluated in glass and plastic containers. The effect of in-line filtration on trace-element concentration was also studied. Individual metal-ion concentrations, pH, color, and clarity were measured at 0-, 12-, 24-, and 48-hour intervals following mixture in TPN, 5% dextrose injection, 0.9% sodium chloride injection, and 8.5% amino acid injection (Travasol, Travenol Laboratories). Multiple trace elements were studied in one-liter glass bottles of 5% dextrose and 0.9% sodium chloride injection. Trace-element contaminants were measured in the intravenous solutions and trace-element injections. The four trace-element preparations were added individually and in combination to the solutions in plastic or glass containers. The trace-element admixtures were passed through in-line i.v. filters (IVEX-2, Abbott Laboratories) during a three-hour period at controlled-flow rates. Concentrations of trace elements remained within 99% confidence limits in all i.v. solutions, with both individual trace elements and combinations of the four trace elements. Trace-element concentrations did not change when the admixtures were passed through the in-line filter unit. It is concluded that there are no obvious compatibility problems associated with admixture nor any detectable retention by the i.v. filter of trace elements.