Mohammed Al Bratty

Targeting Peroxisome Proliferator-Activated Receptors Using Thiazolidinediones: Strategy for Design of Novel Antidiabetic Drugs

Thiazolidinediones are a class of well-established antidiabetic drugs, also named as glitazones. Thiazolidinedione structure has been an important structural domain of research, involving design and development of new drugs for the treatment of type 2 diabetes. Extensive research on the mechanism of action and the structural requirements has revealed that the intended antidiabetic activity in type 2 diabetes is due to their agonistic effect on peroxisome proliferator-activated receptor (PPAR) belonging to the nuclear receptor super family. Glitazones have specific affinity to PPARγ, one of the subtypes of PPARs. Certain compounds under development have dual PPARα/γ agonistic activity which might be beneficial in obesity and diabetic cardiomyopathy. Interesting array of hybrid compounds of thiazolidinedione PPARγ agonists exhibited therapeutic potential beyond antidiabetic activity. Pharmacology and chemistry of thiazolidinediones as PPARγ agonists and the potential of newer analogues as dual agonists of PPARs and other emerging targets for the therapy of type 2 diabetes are presented. This review highlights the possible modifications of the structural components in the general frame work of thiazolidinediones with respect to their binding efficacy, potency, and selectivity which would guide the future research in design of novel thiazolidinedione derivatives for the management of type 2 diabetes.

A Fast and Validated Reversed-Phase HPLC Method for Simultaneous Determination of Simvastatin, Atorvastatin, Telmisartan and Irbesartan in Bulk Drugs and Tablet Formulations

The aim of this study was to develop and validate a fast and simple reversed-phase HPLC method for simultaneous determination of four cardiovascular agents—atorvastatin, simvastatin, telmisartan and irbesartan in bulk drugs and tablet oral dosage forms. The chromatographic separation was accomplished by using Symmetry C18 column (75 mm × 4.6 mm; 3.5 μ) with a mobile phase consisting of ammonium acetate buffer (10 mM; pH 4.0) and acetonitrile in a ratio 40:60 v/v. Flow rate was maintained at 1 mL/min up to 3.5 min, and then suddenly changed to 2 mL/min till the end of the run (7.5 min). The data was acquired using ultraviolet detector monitored at 220 nm. The method was validated for linearity, precision, accuracy and specificity. The developed method has shown excellent linearity (R2 > 0.999) over the concentration range of 1–16 µg/mL. The limits of detection (LODs) and limits of quantification (LOQs) were in the range of 0.189–0.190 and 0.603–0.630 µg/mL, respectively. Inter-day and intra-day accuracy and precision data were recorded in the acceptable limits. The new method has successfully been applied for quantification of all four drugs in their tablet dosage forms with percent recovery within 100 ± 2%.

Comparing monolithic and fused core HPLC columns for fast chromatographic analysis of fat soluble vitamins

Abstract HPLC stationary phases of monolithic and fused core type can be used to achieve fast chromatographic separation as an alternative to UPLC. In this study, monolithic and fused core stationary phases are compared for fast separation of four fat-soluble vitamins. Three new methods on the first and second generation monolithic silica RP-18e columns and a fused core pentafluoro-phenyl propyl column were developed. Application of three fused core columns offered comparable separations of retinyl palmitate, DL-α-tocopheryl acetate, cholecalciferol and menadione in terms of elution speed and separation efficiency. Separation was achieved in approx. 5 min with good resolution (Rs > 5) and precision (RSD ≤ 0.6 %). Monolithic columns showed, however, a higher number of theoretical plates, better precision and lower column backpressure than the fused core column. The three developed methods were successfully applied to separate and quantitate fat-soluble vitamins in commercial products.

Ultrafast monolithic HPLC method for simultaneous quantification of the anticancer agents, imatinib and sorafenib: Application to tablet dosage forms

Purpose : To develop and validate a simple ultrafast monolithic high performance liquid chromatography (HPLC) method for the simultaneous quantification of two anti-cancer agents, imatinib and sorafenib, in pure form and tablet preparations. Method : Chromatographic separation was accomplished using Chromolith flash RP-18 HPLC-column (25 - 4.6 mm; macropores, 2 μm; mesopores, 13 – 15 nm). The optimum mobile phase composition of ammonium acetate buffer (10 mM, pH 8.5) and methanol at ratio of 35:65 v/v was used. Effluent flow rate was adjusted to 1.0 mL/min and the analysis was performed at 250 nm wavelength. The developed method was evaluated for specificity, linearity, precision and accuracy. Results : The method offered a linear relationship over the concentration range of 1 - 16 μg/ml (correction coefficient, R 2 = 0.9999) for both analytes. Limit of detection (LOD) was 0.1891 and 0.1888 μg/ml while limit of quantification (LOQ) was 0.6303 and 0.6294 μg/ml for imatinib and sorafenib, respectively. Mean recovery was within 100 ± 2 %. The utility of the new method was demonstrated by its successful use for the analysis of commercially available tablet formulations of both drugs. Conclusion : The developed method is fast and economical, and is being recommended for routine analysis of imatinib and sorafenib in bulk drug and tablet dosage forms in quality control laboratories. Keywords : RP-HPLC, Chromolith, Imatinib, Sorafenib, Validation, Quality control

Simultaneous Estimation of Diphenhydramine Hydrochloride and Naproxen Sodium in Raw and Tablet Formulation by Reverse Phase - High-Performance Liquid Chromatographic Method

Aims: A simple, reproducible method was developed for the simultaneous determination of Diphenhydramine and Naproxen in tablet formulation using reverse phase HPLC method. Methodology: HPLC separation was carried over on Thermo hypersil – keystone C18 (250 x 4.6 mm, 0.5 ) isocratic mode column using a mobile phase comprising a 30:70 (% v/v) of methanol and 0.5 mM phosphate buffer. The detection was proceeded out by UV detector at 270 nm. The linearity range taken for Diphenhydramine and Naproxen were 15 – 35 mcg/ml and 100-500 mcg/ml respectively. Results: The percentage recovery was found to be 99.74% and 101.11% for Diphenhydramine and Naproxen respectively. The amount of Diphenhydramine and Naproxen found in tablet was Original Research Article 25.006 mg and 219.07 mg respectively. of Diphenhydramine and Naproxen Diphenhydramine and 4.9 minutes for Naproxen Conclusion: The proposed method shows very less time consuming analysis. The proposed method of analysis shows good separation at less retention time and less cost. The developed method can be successfully applied for the determination of bulk powder and combined tablet dosage form.