Identification and Characterization of Hydrolytic Degradation Products of Cefditoren Pivoxil using LC and LC-MS/TOF.

The present research work was carried out to determine stability of cefditoren pivoxil, an orally absorbed prodrug that is rapidly hydrolysed by intestinal esterases to the active cephalosporin cefditoren. Cefditoren was subjected to stress conditions recommended by the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use guideline Q1A (R2). Cefditoren pivoxil was susceptible for degradation under acidic, alkaline and neutral hydrolytic conditions while it was stable under photolytic and thermal stress conditions. Separation of cefditoren and degradation products were carried out by using HPLC. The unknown degradation products were characterized by liquid chromatography-mass spectrometry/time of flight studies. Structures were proposed for each fragment based on best possible molecular formula and complete degradation pathways were reported for cefditoren and its degradants.

Design of selective TACE inhibitors using molecular docking studies: Synthesis and preliminary evaluation of anti-inflammatory and TACE inhibitory activity.

Tumor necrosis factor-α (TNF-α) converting enzyme (TACE) has been considered one of the principal therapeutic targets for the treatment of TNF-dependent pathologies. Several TACE inhibitors have been reported, but none of them has been successfully passed to phase II clinical trials. In the present work, we attempted to design highly selective new non-hydroxamate sulfonamide TACE inhibitors. The docking study was performed on one of the crystal structures of TACE, selected based on its resolution and R value, to tackle the flexibility issue of the active site. The results allowed us to distinguish the analogues with a higher binding affinity toward the active site of TACE and to identify the substituent of analogues needed for binding with the surrounding site of the enzyme. Finally the analogues were docked on crystal structures of six different matrix metalloproteinases (MMPs) for a selectivity study of TACE over MMPs. Some of these analogues were synthesized and subjected to preliminary testing for in vivo anti-inflammatory activity and TACE inhibitory activity.

A validated RP-HPLC method for quantitative determination of related impurities of ursodeoxycholic acid (API) by refractive index detection.

An isocratic RP-HPLC method was developed and validated for quantitative determination of ursodeoxycholic acid (UDCA) and its related impurities. Considering the lower molecular absorptivity of UDCA, refractive index detector was used to detect the impurities on a Phenomenex Luna C(18), 150 mm × 4.6 mm, 5 µm column. The mobile phase was 0.1% acetic acid/methanol (30:70, v/v) and flow rate was 0.8 ml/min. The detector and column temperature was maintained at 40°C. The method is linear over a range of 0.25-3.5 µg/ml for all impurities and coefficient of correlation (r(2)) was ≥0.9945. The accuracy of method demonstrated at three levels in the range of 50-150% of the specification limit and recoveries were found to be in the range of 97.11-100.75%. The precision for all related impurities was below 3.5% R.S.D. The method was applied to commercial bulk drug sample for assay purpose.

Design, synthesis and pharmacological screening of potential anticonvulsant agents using hybrid approach.

A series of 9H, 10H, 3-[N- 4 methyl -2-benzamido thiophen 3-yl carbonyl amino [2-(2'-phenyl 1'- ethylenyl)] 10-(aryl) thiazolidino [4, 5-b] 1, 5 benzodiazepine [7a-7h] were designed and synthesized to meet the structural requirements essential for anticonvulsant activity. Anticonvulsant activity was determined after intra-peritoneal administration to mice by supramaximal electroshock seizures model and Isoniazide Hydrazone induced seizures model. Motor impairement was determined using actophotometer and rotarod apparatus. Among the synthesized compounds two [JG 7a and JG 7e] compounds exhibited significant anticonvulsant activity after intra-peritoneal administration. Active compounds carry hydroxy substitutent at 2-position and methoxy at 4-position in the phenyl ring at C(5) of benzodiazepine. In present we study conclude that small polar and electron rich groups contribute significantly for anticonvulsant activity while electronegative substitutents showed lesser contribution for anticonvulsant activity.

Simultaneous determination of rabeprazole sodium and itopride hydrochloride in capsule dosage form by spectrophotometry.

Three methods viz. Absorbance Ratio Method (I), Dual Wavelength Method (II) and First Order Derivative Spectroscopic Method (III) for simultaneous estimation of Rabeprazole sodium and Itopride hydrochloride have been developed. The drugs obey Beer's law in the concentration range 2-20 microg/ml for RAB and 5-75 microg/ml for ITO. The results of analysis of drugs have been validated statistically and by recovery studies.