Validation Samples, Quality Controls, and Assay Range

Validation Samples, Quality Controls, and Assay Range 

While a substitute matrix can be used to prepare standard cahbrators for a drug compound that exists endogenously, VS/QCs should be prepared in the authentic matrix, regardless. VS data are used during method validation to characterize the intra- and inter-mn accuracy/precision and stability. QC data are used for assay performance monitoring and to accept or reject a run during in-study validation. 

For pre-study validation, no validation batch should be rejected, unless with assignable causes. VS from a pre-study validation can be used later as QC samples. 

VS/QCs should be prepared independently from the standard calibrators. Five or more levels of VS, including the low limit of quantitation (LLOQ), low, mid, high, and upper limits of quantitation (ULOQ) concentrations are often prepared. 

The three concentrations at low, mid, and high within the curve range can be retained for in-study QCs. For analytes that exist endogenously, matrix from multiple individuals should be screened with a preliminary method to identify lots with low or undetectable analyte concentrations. The samples may be pooled and aliquots spiked with varying amounts of reference material to create various concentrations of VS and QC samples. 

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