Problem

Since the FDA guidance on method validation does not permit stripping of matrix to remove endogenous compounds, assays for these analytes hinge on finding depleted matrix for system calibration (preparation of standards and QCs). In the case of Citric Acid, exceedingly high levels exist in human urine.

Proposal:

In consultation with the FDA, we proposed a novel approach of placing sealed dialysis bags, containing selected enzymes, into urine for depletion of Citric Acid.

Outcome:

The approach was highly effective, removing Citric Acid to trace levels for the preparation of standards and Quality Control pools. Results using this technique have been presented at ASMS and AAPS.

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