SPECTROPHOTOMETRIC METHOD FOR THE DETERMINATION OF AMIKACIN IN PURE AND PHARMACEUTICAL DOSAGE FORM

Objective: The aim of the study was to develop an easy, sensible and rapid method for the estimation of amikacin in both pure and marketed formulation using the spectrophotometric method.Methods: Due to lack of chromophoric group in the amikacin, it was derivatized with 0.1 mmol chloranillic acid reagent. For the estimation of amikacin, Shimadzu UV-1700 model spectrophotometer with UV probe software was used. The method was based on simple charge transfer complexation of the drug with a p-chloranillic acid reagent to give a purple coloured product which was measured at 524nm against blank solution.Results: The derivatised product of amikacin was detected at a wavelength of 524 nm. Linearity was observed with the concentration range of 20-100 µg/ml with a regression coefficient of 0.9803. Results of all the parameters were within the acceptance criteria with % RSD less than 2.Conclusion: The spectroscopic method was validated as per ICH guidelines and was found to be applicable for routine quantitative analysis of amikacin in marketed formulations also. The results of linearity, precision, accuracy LOD and LOQ were within the specified limits. The method is highly sensitive, robust, reproducible and specific.Â

DESIGN, SYNTHESIS, IN VITRO ANTIOXIDANT AND IN VIVO ANTI-INFLAMMATORY ACTIVITIES OF NOVEL OXADIAZOLE DERIVATIVES

Objective: In the present study, a series of novel 1,3,4-oxadiazole derivatives (3a-3q) were designed, synthesized and evaluated for antioxidant and anti-inflammatory activities.Methods: The title compounds were designed and docked onto the COX-2 enzyme (3LN1) protein using SYBYLX 2.1. 2-substituted-5-(5-nitrobenzofuran-2-yl)-1,3,4-oxadiazole derivatives (3a-3p) were synthesized from acid catalyzed dehydrative cyclization of 5-nitrobenzofuran-2-carbohydrazide (2) with various heteroaryl/aryl/aliphatic carboxylic acid derivatives. And 5-(5-nitrobenzofuran-2-yl)-1,3,4-oxadiazole-2-thiol (3q) was synthesized on reacting the hydrazide derivative 2 with carbon disulfide. The synthesized compounds were evaluated for in vitro antioxidant property by DPPH radical scavenging assay method and in vivo anti-inflammatory activity by carrageenan induced paw edema method.Results: The synthesized 1,3,4-oxadiazole derivatives (3a-3q) were characterized on the basis of LCMS, 1HNMR [13]CNMR, IR and elemental analysis. The title compounds 3a-3q exhibited significant antioxidant efficacy ranging from 34 to 86%and the results of anti-inflammatory evaluation revealed that compounds 3c, 3e and 3d exhibited substantial anti-inflammatory activity of 72, 68 and 65%, respectively, at a dose of 50 mg kg-1.Conclusion: A significant correlation was observed between the in silico study and the anti-inflammatory results. The anti-inflammatory results highlight the synthesized compounds 3c, 3e and 3d could be considered as possible hit as therapeutic agents.Â

DETERMINATION OF OCTANOL-WATER PARTITION COEFFICIENT OF NOVEL COUMARIN BASED ANTICANCER COMPOUNDS BY REVERSED-PHASE ULTRA-FAST LIQUID CHROMATOGRAPHY

Objective: The present study aims at the development of a reversed phase ultra-fast liquid chromatography (RP-UFLC) method for measurement of the lipophilicity (log P) between n-octanol and water for the newly synthesized coumarin derivatives in our laboratory.Methods: The synthesized compounds were dissolved in methanol and analyzed using XTerra RP18 column as the stationary phase and a mixture of methanol (0.25% v/v octanol) and buffer as the mobile phase with isocratic elution.Results: In this study we concentrated on the relationship between a reversed-phase ultra-fast liquid chromatography (RP-UFLC) retention parameters and log P of our synthesized compounds. Furthermore, a good correlation and very close values were obtained between the experimentally determined log P values and values obtained from Chemdraw.Conclusion: The developed method was found to be insensitive to any of the impurities present and moreover it requires very little sample for analysis

VALIDATION OF STABILITY INDICATING ULTRA-FAST LIQUID CHROMATOGRAPHY METHOD FOR SIMULTANEOUS ESTIMATION OF ATENOLOL and NIFEDIPINE IN BOTH BULK AND PHARMACEUTICAL DOSAGE FORMS

Objective: The study depicts improvement of ensuing validation of a stability indicating technique for the simultaneous estimation of Atenolol and Nifedipine using Ultra-fast liquid chromatographic method (UFLC).Methods: The analysis is performed on Phenomenex Kinetex C18, (150 × 4.6 mm, 5μm) column using methanol and 0.1%ortho-phosphoric acids (75:25 v/v) as mobile phase with a flow rate of 1.3 ml/min. The eluents were checked with PDA detector at 237 nm.Results: In this optimized conditions Atenolol and Nifedipine elutes at a retention time of 2.79 and 4.50 min respectively individually the considered optimized condition is having linearity in the range from 10 to 50µg/ml of Atenolol and 4-20µg/ml of Nifedipine. The method was validated by following the ICH guidelines and their combination drug yield was exposed to acid and base stress, thermal stress, photolytic stress, hydrolytic stress, and oxidative stress conditions. All samples were studied by the given optimized method. In this Calibration curves were linear over studies ranges with correlation coefficient found between the ranges of 0.99 to 1.00.Conclusion: The proposed method was found to be accurate, precise, and specific and suitable for determination of both the drugs

In silico and antithrombotic studies of 1,3,4-oxadiazoles derived from benzimidazole

In the present study, a series of 1,3,4-oxadiazole derivatives (4a-4k) derived from benzimidazole were docked onto factor Xa (PDB: 1NFY) protein using SYBYLX 2.1. and also evaluated for in vitro clot lysis for thrombolytic activity. The synthesized molecules were also screened for in silico ADME studies. The molecular docking studies highlighted that the molecules showed high affinity towards 1NFY with higher docking score and the in silico ADME results were promising and indicated that the molecules holds great potential as a drug candidate. The thrombolytic evaluation was performed for decrease in solid clot weight by the clot lysis study at a concentration of 6.25, 12.5 and 25 µM strengths, respectively. The results of in vitro clot lysis for thrombolytic evaluation revealed that the tested compounds 4a-4k exhibited significant clot lysis with respect to negative control phosphate buffered saline and in comparison to the reference drug streptokinase (30,000 IU). Among all the tested compounds, compound 4j, 4d and 4g exhibited potent thrombolytic activity with EC50 value of 16.2, 18.1 and 23.7 µM, respectively. The thrombolytic efficacy investigation highlights that the synthesized compound 4j could be considered for further clinical studies to ascertain its possible hit as thrombolytic agents