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Quantitation
of analytes requires the development of an analytical method optimized
for precision and accuracy. For LC/MS methods, this requires
appropriate selection of an internal standard, solvents for sample
preparation (typically extraction, concentration and reconstitution)
and LC mobile phases, analytical columns, liquid flow rates, gradients,
ion polarity, daughter ions (for tandem MS measurements), gas flow
rates and other general MS parameters. For some compounds, LC/MS may
not be the most appropriate method of quantitation, and an alternative
detection method (UV, electrochemical, fluorescence, etc.) should be
considered. Proper method development ensures appropriate
chromatographic peak shapes, optimal sensitivity and reproducibility of
results. Full validation of the newly developed method, based on the
Guidance for Industry, Bioanalytical Method Validation published by the
Food and Drug Administration, is completed for all work involving
clinical trials and is recommended for all methods producing results
intended for publication. The PhASR staff is experienced in the
development and validation of LC/MS methods and will provide this
service to its clients. The PhASR can also utilize published
quantitative methods, when available, as a starting point to save time
and cost in method development and validation. PhASR staff will request
a 5 mg sample of the compound of interest (and a structural analog, if
available) from the investigator or will purchase the compound from a
commercial source to use in method development. Once complete, a method
development/validation report will be provided to the PhASR client. The
PhASR will commit to develop methods, without charge to individual
investigators, for all compounds currently being investigated in
clinical trials at OSU (as of October, 2005).
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