Bioanalysis of Endogenous Isotretinoin in Altered and Unaltered Human Plasma by Liquid Chromatography-Tandem Mass Spectrometry Coupled with Electrospray Ionization.

Bioanalytical method development and validation of endogenous Isotretinoin with Isotretinoin D5 as internal standard was done as per current regulatory guidelines. The method is simple, rugged and sensitive enough to estimate endogenous Isotretinoin using the chromatography-tandem mass spectrometry technique. An alternative approach has been adopted for quantitative analysis of endogenous Isotretinoin in human plasma. Isotretinoin free matrix (surrogate matrix) was prepared and further used for the development and validation of Isotretinoin. The method was validated in altered and unaltered plasma. The chromatographic optimization was done with column (ACE C18, 100 × 4.6 mm I.D. 5 µm particle size), using a mobile phase containing 1 mM ammonium acetate, pH 3.0 as a solvent A and solvent B (1 mM ammonium acetate (pH 3.0) with acetonitrile in a ratio of 10:90). A flow rate was set at 0.75 mL/min in a binary gradient mode. The analyte was recovered by liquid-liquid extraction method with diethyl ether as an extraction solvent. Multi-reaction monitoring mode in negative polarity was implemented for the quantification of endogenous Isotretinoin in plasma. The calibration curve of Isotretinoin was linear (r2 > 0.9992) over the concentration range of 0.5-1000 ng/mL. The intra-day precision was found in a range of 2.0-3.9% CV for altered samples and 0.9-3.7% CV for unaltered samples. The inter-day precision was found 2.6-6.1% CV for altered samples and 1.3-3.8% CV for unaltered samples. The average recovery of the extraction procedure was found 64.6% for altered samples and 62.2% for unaltered samples.

Solubility enhancementofcefixime trihydrate by solid dispersions using hydrotropic solubilization technique and their characterization

Abstract The aqueous solubility of cefixime trihydrate (a water insoluble drug) using different hydrotropic agents was determined and solid dispersions of cefixime trihydrate were prepared by hydrotropic solubilization technique. The drugs content were determined. The aqueous solubility of v was increased many fold in presence of sodium acetate trihydrate as hydrotropic agent. This hydrotropic agent was used to prepare solid dispersion of cefixime trihydrate. Cefixime trihydrate and sodium acetate trihydrate were accurately weighed and taken in a 200 mL beaker. Distilled water 10-15 mL was taken to dissolve hydrotropic agent using heat (48-50 °C). The drug was then added to it and magnetically stirred till whole mass get viscous. The solid dispersions of cefixime trihydrate were characterized by XRD, DSC and IR studies. DSC thermogram, XRD and Infra-Red spectra were studied. Solid dispersions, thus prepared, showed faster release of the drug as compared to pure drug and physical mixture.