Mass Balance

[KRichardson]

Hi,

What would the industry specification on 'Mass Balance'.

We are working on a new method and from what we have see there is a difference of 2.42% (w/w) between the main peak and its impurities. Is this difference acceptable or are there limits to decide if something is in mass balance?

Thanks

K

[Rob Burgess]

So what you are saying is that you have a label claim assay result of about say 98% but your impurities % w/w of 4.5%. Is this correct or is it the other way round.

Assuming you are basing your analysis on % w/w results have you worked out response factors for your individual impurities (assuming you have them to hand?).

My gut feeling feeling is that mass balance discrepancies of between 2-5% are perfectly acceptable. Anything over 10% then I'd start to worry. Not sure if there is any definitive guidance on this topic within the FDA or ICH. There might well be, but it may be called something else other than "mass balance".

Any other thoughts / comments on this?

[Dan]

I know of no guidance given anywhere for mass balance.

I agree with Rob; a 2.5% dicrepency (high or low) is not significant.

Regards,
Dan

[JM]

Most of the time the "mass balance" in degradation studies does not correlate due to several reasons.

One often assumes, that the percent of degradant formed corresponds to the percent parent drug degraded. This assumption would be invalid , if,

1The degradant had a molecular weight that differed significantly from that of the parent drug.
2.Difference in UV response factor.
3.Generation of Non-UV active impurities including gases .
4. Method not capable of detecting all impurities due to non-elution or different UV max for impurities.

we normally make attampt to correlate mass balance and include results in stress testing.

JM