Pharmaceutical products - Stability study & Mass balance concerns

Pharmaceutical products - Stability study & Mass balance concerns

Mass Balance concept  Assay of parent Product + % impurities ~ 100%

Mass balance is the process of adding together the assay value and levels of degradation products to see how closely these add up to 100% of the initial value, with due consideration of the margin of analytical error. In other words Mass balance correlates the measured loss of potency (i.e assay) to the measured increase in the amount of degradation products. If the loss in potency can be reasonably accounted for by the amount of degradants measured, then mass balance is achieved.

Mass balance is to be achieved at least up to 95% level.

 With respect to an analytical method, the term 'mass balance' divulge to its ability to analyse the degradation products of a pharmaceutical product. The assessment of degradation in pharmaceutical products involves two aspects of analytical testing.

1.   Availability of specific or selective analytical method for accurate assay testing of pharmaceutical product, in order to measure any loss.

2. Availability of specific or selective analytical method for quantification of all the degradation products formed. Ideally, when degradation occurs, the measured amount of potency  loss should correlate the increase in degradation products. This correlation is referred to as “mass balance”

 For example, a 25% assay drop of potency (i.e assay) and only 8% increase in degradation products, it is likely that additional degradation products formed are not accurately determined by the given method.

A method is considered to have 'good' mass balance if:

v It can quantify the loss in amount of drug molecule due to degradation (which should result in a lower assay value),

v It can detect and quantify the degradation products formed during degradation of the drug molecule, and

v The amount of the drug lost is equal to the amount of degradation products formed.

Mass balance issue can arise due to following reasons

v Poor understanding of degradation pathways of a parent drug

v Inadequate/poorly developed analytical method.

Unknown degradation products could be toxic and can affect safety and efficacy of the pharmaceutical product, so it is noteworthy to have methods that detect all major degradation products. In short, safety is the prime aspect for the study of mass balance.