Demonstrating Assay Control
Modern HPLC-MS/MS methods for drug quantitation are highly sensitive owing to the high selectivity of tandem mass spectrometry. The chemical selectivity and the ruggedness of atmospheric pressure ionization sources also allow for very short sample cycle times.
Unfortunately, this high performance capability must be monitored closely to ensure the quantitation process remains under control. The need for tighter control has recently been emphasized by regulatory bodies and was a key topic at the Joint AAPS/FDA meeting in 2006 ("Crystal City III").
"A proper evaluation of incurred sample reproducibility and accuracy needs to be performed on each species used for Good Laboratory Practice (GLP) toxicology experiments."
The conference report from the 2006 meeting and follow-up meetings indicate that there is a strong expectation that all studies submitted for both preclinical and clinical analysis must provide evidence that the assay is under control.
It is up to study sponsors to ensure that work done both internally and by contract research organizations meets the reproducibility expectations of the regulatory agencies.
The requirement of performing incurred sample reanalysis as the primary method for demonstrating control during study sample processing was clearly stated at the recent AAPS GLP meeting by FDA officials.
Rubicon Sample Reanalysis and Review
The Rubicon system now includes tools to perform rigorous statistical analysis on study samples selected for repeat analysis with a simple and easy to use interface.
The Rubicon Data Explorer is capable of performing Mean-Difference Plots as described by Bland and Altman.
Because Rubicon converts mass spectrometry and chromatography data into an open format, the analysis can be performed regardless of the instrument type.
The technique is also very powerful in analyzing cross-validation studies between labs and during method transfer.
In addition to plots and interactive analysis,
Rubicon can generate PDF files for inclusion
in written reports. And due to the numerical
stability of the Data Explorer, the open format of
the raw data, and the simplicity of locating data on
the central server, Rubicon ensures that all previous
study data can be reanalyzed for as long as needed -
without the worry of instrument obsolescence or data
loss.
Download an Example PDF
Report for review.
