Quantitative Open-Access HPLC Analysis - Pharmaceutical Technology

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Quantitative Open-Access HPLC Analysis
The authors discuss the approach taken to develop a new calibration approach, its associated protocols, and how it can be used to calculate data.


Pharmaceutical Technology
Volume 34, pp. s6-s11


BORMAN ET AL.
The use of open-access high-performance liquid chromatography (HPLC) systems in drug discovery and pharmaceutical development has steadily increased during the past decade. This growth has enabled chemists and engineers to perform a large proportion of their own analysis without dedicated support from analytical scientists. Within chemical development at GlaxoSmithKline (GSK), for example, about half of chromatographic analyses (250,000 samples per year) are performed by process chemists or chemical engineers using open-access systems. The uptake of these systems has been high and the application of traditional techniques for monitoring reactions such as thin-layer chromatography (TLC) has been superseded in chemical development at GSK. Implementation of a novel, global open-access approach using generic fast-LC and custom analytical methods on more than 100 HPLC-ultra-violet (UV) instruments has been described by Roberts et al. (1).

Most HPLC open-access systems within chemical development laboratories are used to generate impurity-profile information using area–percentage responses on non-quality critical samples of active pharmaceutical ingredients (APIs), intermediates, and starting materials. In addition to obtaining this data, synthetic chemists must generate purity data on samples to support route- and process-development. A new tool developed by GSK, the Yieldaliser, enables the rapid and reliable estimation of yields in solution and assays of isolated solids (in addition to generating impurity profiles) without any requirement for the user to prepare standards. The authors discuss the calibration approach, which is performed using an unrelated standard material analyzed at an optimal wavelength which may be different to the compound of interest.

External standardization across different wavelengths

Several standardization methods were investigated during the development of the tool with a focus on automation. External and internal standardization were explored using single and multiple standard sets, which were analyzed at a single wavelength or multiple wavelengths. To analyze compounds that contain chromophores in the typical UV range used in HPLC (210–300 nm), the standard and sample compound had to be analyzed at their respective λMax or λOpt (i.e., the most optimal/robust region within the UV spectrum). Additional functionality was integrated into the open-access HPLC platform (this term is used by Roberts et al. to describe a collection of actively managed and supported open-access instruments [1]), which enables chemists and engineers to perform their own assay analysis.

To generate assay data on a particular compound using the platform, an analytical chemist (i.e., the lead user) must first determine an accurate response factor for the compound of interest (analyzed using the compound's λOpt) against the benzophenone external standard (analyzed using its λmax). The Yieldaliser software uses the response factor in its calculations.


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