Effects of vitamin D on insulin secretion and glucose transporter GLUT2 under static magnetic field in rat.

The present study investigated the effects of vitamin D supplementation on insulin secretion and glucose transporter following static magnetic field (SMF) exposure in rat. Wistar male rats were divided into the following groups: control, SMF-exposed rat (128 mT; 1 h/day for 5 days), vitamin D-treated rats (1600 IU/100 g, received by gavage for five consecutive days), and co-exposed rats (the last day and after exposure rats received a single dose of vitamin D per os). Our results showed that exposure to SMF induced an increase in plasma glucose level and a decrease in plasma insulin concentration. Moreover, ß cell insulin content and islet area were lower in SMF-exposed group compared to control. Likewise, we reported the absence of GLUT2 expression in extracellular membrane of pancreatic islet in SMF-exposed group. Interestingly, supplementation with single dose of vitamin D per os corrected insulinemia and glycemia disturbances caused by SMF. By contrast, the same treatment failed to correct pancreatic area. This study provides evidence that vitamin D supplementation has curative effect on pancreas insulin content and on GLUT2 disruption caused by SMF exposure.

Validated micellar electrokinetic capillary chromatography method for quality control of the drug substances hydrochlorothiazide and chlorothiazide.

A stability-indicating, quality control analysis method was developed and validated for the diuretic drug substances hydrochlorothiazide (HCTZ) and chlorothiazide (CTZ). Micellar electrokinetic capillary chromatography employing the anionic detergent sodium dodecyl sulfate at 30 mM in 20 mM sodium borate buffer pH 9.5 was utilized to separate and quantify the active drug substance HCTZ from CTZ and the common impurity, 4-amino-6-chloro-1,3-benzenedisulfonamide (DSA). A 100 microns I.D. uncoated fused-silica capillary was necessary to provide the sensitivity, i.e. 1 microgram/ml, for quantification of the DSA impurity. In this study, the linearity, precision, selectivity, accuracy, reproducibility and limit of quantitation for the method were investigated for HCTZ, CTZ and DSA. As the first validation of a drug substance method by capillary electrophoresis in this laboratory, unusual care was taken to insure reliability and ruggedness with multiple instruments, capillaries and analysts. Precision and reproducibility in the range of 1% R.S.D. was achieved by controlling subtle injection factors. These included minimizing the time in which the capillary ends were not immersed in buffer or sample during the injection process and minimizing the number of assays for each anode or inlet buffer vial. Stacking induced by differences in ionic strength between sample and capillary buffer was reduced by using a sample buffer concentration similar to that of the capillary buffer. Although stacking accomplished by using lower sample buffer concentrations increased sensitivity, reproducibility was decreased. Achievement of the 1% R.S.D. precision level means that many quality control assays for drugs with good absorbance characteristics can be validated with HPLC reproducibility and CE efficiency. These micellar electrokinetic capillary chromatography methods conform to the USA and European Pharmacopoeial validation guidelines.

Mixed ion pair liquid chromatography method for the simultaneous assay of ascorbic acid, caffeine, chlorpheniramine maleate, dextromethorphan HBr monohydrate and paracetamol in Frenadol sachets.

The five active drug substances and two of the excipients present in Frenadol, a cold medication, were separated. The active drug components dextromethorphan HBr monohydrate, ascorbic acid, caffeine, paracetamol and chlorpheniramine maleate were quantitatively assayed by a mixed ion pair LC method. The excipients separated were citric acid and maleic acid. The HPLC assay included dual-wavelength detection to simultaneously quantify the large concentration of paracetamol and the much lower concentration of chlorpheniramine and dextromethorphan. Both tetrabutylammonium hydrogen sulphate (TBA) and pentane sulphonic acid (PSA) were necessary for resolution of the seven compounds. The TBA was necessary to lessen peak tailing for dextromethorphan and chlorpheniramine, to retain ascorbic acid and to shorten assay time. The pentane sulphonic acid enhanced peak shape for dextromethorphan and chlorpheniramine. The assay of the active drug substances was validated for use in quality control applications. Validation studies demonstrated that the procedure was accurate, linear, precise, reproducible and rugged. The method conformed to both USP and EC validation guidelines.

Nonlinear chromatography Recent theoretical and experimental results.

The theory of nonlinear chromatography has been advanced by the incorporation of recent results obtained by the theory of partial differential equations. The system of equations of the ideal model has been solved analytically in the case of a single component for which the equilibrium isotherm between the mobile and the stationary phases is given by a Langmuir equation. A series of computer programs has been written which permits the calculation of numerical solutions of the semi-ideal model. The properties of the solutions obtained are described and discussed for a one-component system (profile of high concentration bands of a pure compound eluted by a pure solvent), several two-component systems (elution of a pure compound band by a binary mobile phase, separation of a binary mixture eluted by a pure mobile phase), and three-component systems (separation of a binary mixture eluted by a binary solvent, displacement and separation of a binary mixture). Experimental results are reported which validate the conclusions derived from the numerical integration of the model. The conclusions of the work apply to all high-performance chromatographic procedures, i.e., to those where the kinetics of mass transfer are fast enough for the mobile and stationary phases always to be near equilibrium. More specifically, the contribution from the kinetics of the retention mechanism to the mass transfer resistance must itself be negligible. This clearly excludes affinity chromatography.