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We have reason to believe we are looking at a drug that seems to be reacting with endogenous formaldehyde (it traps it with two nearby nucleophiles forming a fairly stable adduct). It happens on the bench top in spiked plasma but also seems to be produced in vivo (preclinical species) and has a metabolite-like profile (increases then decreases in concentration over time)
I'm wondering if there are any known toxicological implications of this type of reactivity or what type of experiments I should run to test this.
I'm also wondering if there are any bioanalytical tricks to prevent ex-vivo reaction with any endogenous formaldehyde in the PK samples and the spiked plasma. We currently have some stability-like experiments going to probe this but we know that in the autosampler, even quenched with organic, we get adduct formation over time.
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The following message was posted to: PharmPK
Tarra,
Collect the plasma samples over hydroxylamine to react all the endogenous
formaldehyde.
Dale
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