A simple and efficient approach to reversed-phase HPLC method screening.

The development and utility of an efficient HPLC method screening strategy using only four columns for the separation of pharmaceutical compounds and related impurities is presented. The strategy established a two-column approach to enable rapid early method development, along with a four-column approach for commercial method development of the analytical methods utilized to verify the quality of drug substance or drug product. Mobile phases consisted of acetonitrile or methanol with aqueous trifluoroacetic acid for low pH screening, and ammonium hydroxide for high pH screening. Examples are provided to demonstrate the practicality and orthogonality of the method screening process. A unique system suitability check, using commercially available compounds, was incorporated as a tool for troubleshooting and for ensuring adequate system performance prior to screening. Initial testing of the strategy revealed that the columns chosen were successful in leading to assay and impurity methods for 40 pharmaceutical compounds.

3-(Triethoxysilyl)propionitrile sol-gel coating.

3-(Triethoxysilyl)propionitrile (TESPN) sol-gel has been prepared under different conditions. It was employed for coating the surfaces of quartz and aluminum. Infrared (IR) and Raman spectra of TESPN and TESPN sol-gels have been recorded in the study of the sol-gel process. Transmission and reflection absorption IR (RAIR) spectra of TESPN sol-gel coated quartz and aluminum have also been collected for better understanding the film formation on the substrate surfaces. Spectra collected at different temperatures indicated that the silane film on quartz decomposes at 700 degrees C. Results from thermal gravimetric analysis (TGA) supported this result. Based on the group frequencies and the spectral behavior in different states, some vibrational modes were assigned to the observed bands. The anticorrosion behavior of the sol-gel coated aluminum in comparison with the uncoated metal was evaluated by measuring the potentiodynamic polarization and electrochemical impedance spectra (EIS).

Vibrational spectroscopic studies of vinyltriethoxysilane sol-gel and its coating.

Infrared and Raman spectra of vinyltriethoxysilane (VTES), the VTES sol-gel, and the sol-gel coated aluminum have been collected. The assignments of the vibrational modes for the silane, the sol-gel, and the sol-gel films have been made based on the group frequencies and the spectral variation collected at different physical and chemical states of the sol-gel samples. Applying the sol-gels onto the metal grids allowed the drying and the high temperature treatment of the samples for the collection of infrared transmission spectra. From the variation of the sol-gel and the sol-gel coated aluminum IR spectra with temperature, it was noticed that the samples partially decomposed when the temperature was higher than 100 degrees C. Electrochemical experiments have demonstrated that the anticorrosion property of the coated aluminum has significantly increased. The water and the hexadecane contact angle measurements showed that the surface modified metal had a much higher hydrophobic property than the untreated metal.

Development and application of a universal method for quantitation of anionic constituents in active pharmaceutical ingredients during early development using suppressed conductivity ion chromatography.

A universal method for quantitation of anionic substances in active pharmaceutical ingredients (API) during early development was developed using ion chromatography (IC). The method was developed to allow rapid characterization of APIs in support of early clinical studies The method parameters were chosen to allow quantitation of monovalent, divalent, and trivalent inorganic ions as well as monvalent and divalent carboxylic acids. These parameters were also chosen to ensure appropriate performance for regulated analyses using less than 10mg of API per replicate. The method was applied to and validated for a range of anionic analytes in APIs of varying hydrophobicity to demonstrate applicability to various analyses encountered during early development of pharmaceuticals.

Systematic development and validation of stability indicating micellar electrokinetic chromatography methods for early stage drug candidates.

Suitable methods for assessment of purity, potency and stability of new drug substances and drug products are required to be rapidly developed and validated to provide appropriate data for early project development decisions. In order to routinely provide methods of consistent and suitable quality to meet increasingly aggressive timelines, systematic approaches to both develop and validate analytical technologies have been developed. Systematic approaches to evaluate separation parameters such as buffer pH, buffer ionic strength, surfactant concentration, organic modifiers, organic modifier concentration, applied voltage and temperature were evaluated for an early stage drug candidate. Techniques to improve method precision and ruggedness were also examined. Finally, the validation results from the micellar electrokinetic chromatography method utilizing an internal standard were compared against the simultaneously developed high-performance liquid chromatography method.