Development and validation of a stability-indicating RP-HPLC method of cholecalciferol in bulk and pharmaceutical formulations: Analytical quality by design approach

The present article utilized analytical quality by design (AQbD) methodology to optimize chromatographic conditionsfor the routine analysis of Cholecalciferol (CHL). Taguchi orthogonal array design and Box–Behnken designwere employed to screen and optimize critical method parameters for augmenting the method performance. Theoptimal chromatographic separation was attained on Eurosphere® 100-5, C8 (250 × 4.6 mm i.d., 5 μm) column in anisocratic elution mode using methanol:acetonitrile (50:50, % v/v) as mobile phase at a flow rate of 1.0 ml/minutesand photodiode array detection at 265 nm. The optimized chromatographic method was successfully validated asper International Council for Harmonisation Q2 (R1) guidelines. The method was found to be linear (r2 = 0.9993)in the range of 20–100 IU/ml. Limit of detection and limit of quantitation were found to be 10 and 20 IU/ml. Theprecision, robustness, and ruggedness values were within the acceptance limits (relative standard deviation < 2). Thepercent recovery of in-house developed 400 IU mouth dissolving tablets and marketed Tayo 60k tablets were foundto be 99.89% and 101.46%, respectively. The forced degradation products were well resolved from the main peaksuggesting the stability-indicating the power of the method. In conclusion, the AQbD-driven method is highly suitablefor analysis of CHL in bulk and pharmaceutical formulations

Evaluation of the influence of fluoroquinolone chemical structure on stability: forced degradation and in silico studies

ABSTRACT Fluoroquinolones are a known antibacterial class commonly used around the world. These compounds present relative stability and they may show some adverse effects according their distinct chemical structures. The chemical hydrolysis of five fluoroquinolones was studied using alkaline and photolytic degradation aiming to observe the differences in molecular reactivity. DFT/B3LYP-6.31G* was used to assist with understanding the chemical structure degradation. Gemifloxacin underwent degradation in alkaline medium. Gemifloxacin and danofloxacin showed more degradation perceptual indices in comparison with ciprofloxacin, enrofloxacin and norfloxacin in photolytic conditions. Some structural features were observed which may influence degradation, such as the presence of five member rings attached to the quinolone ring and the electrostatic positive charges, showed in maps of potential electrostatic charges. These measurements may be used in the design of effective and more stable fluoroquinolones as well as the investigation of degradation products from stress stability assays.

Validated stability-indicating HPLC method for simultaneous estimation of ofloxacin and satranidazole from pharmaceutical dosage form.

The present paper describes development of stability- indicating RP- HPLC method for the simultaneous determination of Ofloxacin and Satranidazole in presence of its degradation products, generated from forced degradation studies. Ofloxacin and Satranidazole and their combination drug product were exposed to acid, base, neutral hydrolysis; oxidation, dry heat, photolytic stress conditions and the stressed samples were analyzed by proposed method. The proposed HPLC method utilizes HiQ sil C18W column (250mm × 4.6mm i.d., 5μm) of KYA TECH, Corporation and a mobile phase comprising of acetonitrile: phosphate buffer (pH3) in ratio of 35:65v/v with flow rate of 1ml/min. The retention time of OFLX and STZ was found to be 2.85min and 6.25min respectively. Quantitation was achieved with UV detection at 296nm for OFLX and 320nm for STZ. The method has been validated for ofloxacin and satranidazole in terms of accuracy, precision, linearity, LOD, LOQ and robustness. The developed validated stability-indicating HPLC method was found to be simple, specific, accurate and reproducible for the determination of instability of these drugs in bulk and commercial products.