( Chromatography and Mass Spect...)Trace Analysis Optimizing Sensitivity Finnigan Surveyor PDA Detector

Chromatography and Mass Spectrometry Application Note

L.Pereira,¹ M.Woodruff,¹ P.Deland,² D.Elmashni,² M.Euerby<sup>3

1</sup>Thermo Electron Corporation, Runcorn,UK
²Thermo Electron Corporation, San Jose CA,USA
³Astra Zeneca R&D, Charnwood,UK

Overview
Comparison of the performance of various diode array detectors in the analysis of trace related substances of a pharmaceutical drug substance are discussed. We consider the variables of stationary phase in the optimization of analysis sensitivity, both by altering selectivity and improving peak shape.

Our results show that by utilizing the total internal reflectance potential of the flow cell in the Finnigan Surveyor PDA that significant increases in the signal/noise ratio can be achieved, therefore leading to improved limit of detection (LOD).

We have also shown how the correct choice of stationary phase both in terms of its quality and its physical characteristics can affect the overall sensitivity of the method.

Introduction
HPLC is widely used in the analysis of trace components, i.e. <0.1%, in complex mixtures. The success of this technique in terms of determining accurate concentrations of impurities relies on gaining good separation and excellent peak shapes for all of the analytes involved. This will be dependent upon system parameters such as sample preparation, column resolution, sample injection, and sample detection. In order to achieve the best measurement accuracy, trace components of interest need to be completely resolved from adjacent peaks.

Quantitation of trace components is regularly performed by measurement of peak height, therefore the chromatographic separation needs to produce sharp, efficient peaks.