Geoffrey S. Rule
ARUP Laboratories,USA
Title: Ultra-reliable LC-MS Methods: Moving mass spectrometry to the core laboratory
Biography
Biography: Geoffrey S. Rule
Abstract
Many clinical laboratory assays are performed every day at high volumes with only limited numbers of calibration standards. This has lead us to ask whether mass spectrometry based assays are stable enough to perform routine patient sample testing without the need for analyzing multiple calibration standards in a batch-wise fashion. To examine overall assay stability we categorize sources of variability into ten separate categories (eg, pipetting and integration errors) and then examine options for reducing overall variability. For example, by making use of a weighted calibration update strategy we have shown that, over a seven month period, we are able to reduce the number of calibration standards analyzed by 80%, over a conventional approach, yet with improved precision for three androgen analytes. The weighting strategy effectively reduces the variance around the calibration curve slope used for quantitation. A second source of variability examined is that resulting from the mass spectrometric determination of analyte to internal standard ratio. In general, we expect this ratio to remain constant during the analytical process but recent studies have shown that partial chromatographic separation of deuterated internal standards can result in differential suppression effects and nonlinear curves. In addition, data presented here shows that the mass spectrometer itself may not always yield the constant area ratios particularly when deuterated internal standards are used. In comparison, we show that 13C labelled internal standards behave better, not only chromatographically, but in terms of MS measurement as well.