Biomedical subjects

Henrik T Rasmussen

Publications and source records attributed to Henrik T Rasmussen.

3 recordsLinked to original sources

PubMed2005

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. The HILIC method is validated and has met all validation acceptance criteria for the support of drug development activities.

Acetonitriles↗

PubMed2004

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. The main focus of the article is on method optimization using experimental designs. A Plackett-Burman design was used to screen multiple method factors including extraction solvent strength, extraction solvent volume, shaking speed of a reciprocating shaker, and shaking time. Later, two of the factors were studied in more details using a 4 x 5 general factorial design. From the experimental results, the so-called main effects plots and interaction plots were generated using a statistical software. The plots are helpful in choosing the method conditions.

Administration, Cutaneous↗

PubMed2003

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. This approach significantly reduces the number of runs in method development. After a satisfactory separation was obtained, we used a method optimization step with Plackett-Burman experimental designs. The purpose of the 16-injection set experiments was to evaluate nine method factors with regard to method precision, accuracy, sensitivity and specificity. The results provided logical justifications in selecting method parameters such as column temperature, detection wavelength, injection volume, and sample solvent, etc. In data analysis, instead of the traditional mathematical manipulations, we used the graphical methods to examine and present data by creating the so-called main effect plots. Because replicates of design points were not run, the data did not allow the testing of statistical significance. However, it provided visual presentations in a way that is easy to understand for the method developer and end user alike.

Chromatography, High Pressure Liquid↗