how to improve low level spiked recovery-urgent!
Posted: Fri Apr 05, 2013 10:46 am
I am validating a drug product impurity method. The spiked recovery was performed by spiking a known impurity at LOQ level (1%), specification limit (3%) and 5% to placebo which contains water, API and mannitol. API was also spiked along with the known impurity to demonstrated recovery of unknown impurity. (for ex: spiked both know imp and API at LOQ level to 40ug/ml mannitol in water). The recovery criteria is 85-115% but the spiked recovery for known impurity failed at LOQ level while API passed.
This is a lyophilized drug and suppose to be reconstituted with water before administered.
Why is the known impurity recovery low at low level? I can only think of two reasons: 1 impurity was binding with mannitol, 2: impurity was not completely dissolved. Either way I think I should look into sample preparation? maybe sonicatethe sample (the sample was not sonicated at the time of prep)?
Pleas advise on how do I improve the recovery? and what could be the reason.
Thanks.
This is a lyophilized drug and suppose to be reconstituted with water before administered.
Why is the known impurity recovery low at low level? I can only think of two reasons: 1 impurity was binding with mannitol, 2: impurity was not completely dissolved. Either way I think I should look into sample preparation? maybe sonicatethe sample (the sample was not sonicated at the time of prep)?
Pleas advise on how do I improve the recovery? and what could be the reason.
Thanks.