Chromatography Forum

Hi All,

i am working in validation deportment,so i have on doubt on preservative validation ( Methyl paraben and propyl paraben-- etc)
1) Is it required forced degradation study for preservative validation?
2) for Specificity experiment we need to spike the impurities at specification levels or 1% level. so which concentration we need to cosider the impurity calculation ?
Thanks
Ashok reddy

1) Is it required forced degradation study for preservative validation?

What is *required* is determined by your company's SOPs. If you are quantitating the excipients, then the forced degradation that you do on the formulation should suffice. If you are looking at a stability indicating assay for the excipients, then a forced degradation is a good idea so you know what you are looking for.

2) for Specificity experiment we need to spike the impurities at specification levels or 1% level. so which concentration we need to cosider the impurity calculation ? Again, a matter of your company SOPS. In principle, for specificity you need enough of the potential interferences to see and to differentiate from the analyte. Your target for the impurities should be commensurate with the amount of risk they pose.

for Specificity experiment we need to spike the impurities at specification levels or 1% level. so which concentration we need to cosider the impurity calculation ?

Again, a matter of your company SOPS. In principle, for specificity you need enough of the potential interferences to see and to differentiate from the analyte. Your target for the impurities should be commensurate with the amount of risk they poseat

what i asked is which concentration we need to consider for impurity calculation,because in my sample concentrati on main anlyte is having concentration about 500 ppm and preservative is habving 100 ppm.

for example impurity speck level is 1%

=500 x1/100 ( with respect to main analyte)
=100 x 1/100( with respect to preservative)

above expressions which one is correct please suggest

regards
ashokreddy

If you are quantitating the API, then the % should be with respect to the API. If you are only quantitating the preservative, then the % should be with respect to the preservative.

Are you sure that the regulations even require testing of the stability of the preservatives CHEMICALLY ? Can't a micobiology department document that the product is preserved over time ?

You can do the preservatives by micro. This involves checking at each time point and for the life of the product for *each* batch produced. Alternately many places choose to do validation on the preservative level needed to insure that the product stays clean for it's shelf life. Then the product can be assayed chemically at point of production and based on the data no extended microbial effectiveness testing is needed. If an issue arises later in the life of a particular batch, a chemical test can be used (faster and cheaper) to determine if the formulation is still preserved.

Back to the original posters question, I agree with Tom. The forced degradation on the finished good should suffice as long as the force degraded samples are run with respect to both preservatives and API.

As a friendly hint, keep methanol away from the the sample preparation when doing the acid forced degradations involving the paraben mixture. I once had to explain to a colleague with a limited organic chemistry background why he had degraded the propylparaben but had greatly increased the methylparaben composition of his sample.

Paul