A novel dosing form of Lidocaine required the quantitation of the parent compound and one key metabolite in plasma, urine and tissue at trace levels (50 pg/g). Prior attempts were unsuccessful at meeting sensitivity, precision and accuracy requirements.
We proposed using a two-stage extraction procedure and dual analyses of the single extracts combined with valve switching to eliminate significant ion suppression in meeting sensitivity requirements.
The resulting methods were successfully validated using this approach. A second complicating factor for this project involved incurred sample repeat (ISR) analysis for rat tissues weighing ≤ 100 mg. In consultation with the FDA, the use of ISR from larger species (dog) were proposed and accepted for rat tissue analyses.