The development of a semiautomated procedure for the synthesis and screening of a large group of molecularly imprinted polymers.

A method for synthesis and evaluation of molecularly imprinted polymers (MIPs) on a semiautomated miniature scale is reported. This technique combines molecular imprinting with the combinatorial chemistry approach, allowing rapid screening and optimizations of libraries of MIPs. The polymers were prepared and evaluated in situ by rebinding utilizing powder dispensing and liquid handling systems.

Orthogonal method development using hydrophilic interaction chromatography and reversed-phase high-performance liquid chromatography for the determination of pharmaceuticals and impurities.

A hydrophilic interaction chromatography (HILIC) method has been developed and validated as a secondary or orthogonal method complementary to a reversed-phase HPLC (RP-HPLC) method for quantitation of a polar active pharmaceutical ingredient and its three degradation products. The HILIC method uses a diol column and a mobile phase consisting of acetonitrile/water and ammonium chloride. The compounds of interest show significant differences in retention behaviors with the two very different chromatographic systems, which are desired in developing orthogonal methods.

Sample preparation optimization for assay of active pharmaceutical ingredients in a transdermal drug delivery system using experimental designs.

A simple but very effective sample preparation method is discussed for a matrix or drug-in-adhesive type of transdermal drug delivery system (TDS). The method is a one-step extraction using a methanol/water solvent system. Because of the unique design and physical property of the delivery system, special considerations were taken in selection of sample solvent, sample container and extraction enhancement device.

Strategy for developing and optimizing liquid chromatography methods in pharmaceutical development using computer-assisted screening and Plackett-Burman experimental design.

We describe a three-step method development/optimization strategy for HPLC assay/impurity methods for pharmaceuticals, which include multiple-column/mobile phase screening using a system equipped with a column-switching device, further optimization of separation by using multiple organic modifiers in the mobile phase, and multiple-factor method optimization using Plackett-Burman experimental designs. In the first two steps, commercially available chromatography optimization software, DryLab, was used to perform computer simulations. This allows the method developer to evaluate each condition (one column/mobile phase combination) with retention data from two scouting gradient runs.