Bioequivalence and Bioavailability Forum

Dear Members,

We have done a two way crossover biostudy (250 mg) on a drug which hydrolyses to its active acid metabolite. As per FDA's recommendations and available literature acid metabolite only has to be quantified.

We have developed and validated method for the acid metabolite in the range of 0.5 to 20 µg/mL based on expected Cmax of 10 µg for 250 mg dose, same dose used for biostudy.

During analysis we have observed that all the samples are below LOQ or just above LOQ, to say Cmax of just 1 µg/mL in both the periods, which is unexpected. All the quality control samples interspersed within the batch are within the acceptance criteria

What could be the problem?

Is it possible that there is no release of drug from the formulation and hence no hydrolysis?

Your comments will be highly appreciated

Thanks

Chirag