“The assay value of drug and total responses of all degradants should equal the initial value i.e. it’s 100% is mass balance”.
Mass balance in the pharmaceutical analysis is very much important. It is representing the degradative losses of parent drug compare well with the measured increase in the degradation products. Equally, if one observes, for example, a 10% loss of parent drug but only measures a 2 % increase in degradation products, it is expected that additional degradation products formed are not accurately determined by the present method(s).
Mass balance is an important consideration in assessing degradation pathways of pharmaceutical products. The related substances or organic impurities method is a stability-indicating method for degradants. it is important to have methods that detect all major degradation products. Thus, safety is the major reason for the study of mass balance.
Mass balance is also useful in method validation. In order to demonstrate that analytical methods are stability-indicating, unstressed, and stressed results were compared and evaluated. Any increase in degradation a product that correlates well with the loss of parent drug, aids in demonstrating that the methods can accurately assess degradation.
Usually, 5 % to 10 % of degradation is looked for as a forced degradation study during the different forced degradative conditions. There is not all compounds/formulations will degrade by 10% under even extreme conditions, however, a sufficient attempt must be taken to promote degradation. Any stability observed from the studies must be scientifically explained and justified in case of low degradation levels (i.e. < 10%). These types of criteria can be used within internal guidance documents where extreme conditions are defined.
During Stress studies it is “good to show the mass balance” but in reality, it is normally not achieved due to the following reasons,
Figure: Fishbone diagram of the major causes of mass imbalance.
Primary aim is to separate related substance degradants from unrelated, to identify key degradation pathways by studying about chemistry to get MS and UV spectra on degradants. Develop a simple method to resolve the degradants from the drug and from each other. Calculating the mass balance from this initial study tells us about how much we know.
We need to explore different detectors like GC/MS, LC/MS, LC-MS-NMR, RI Detector, ELSD Detector for possible degradants. Later steps might include isolation of specific degradants to determine structure and response factors, giving us better understanding of chemistry and a quantitative correction to the degradant’s response.
There is no guideline or industry-accepted practice for mass balance limit for forced degradation studies but we need to demonstrate the mass balance of the method, whatever is achieved if all other validation parameters are OK. Generally, 95 % to 105 % mass balance is well accepted.
The mass balance equation:
Total mass = (Amount of mass remained + Amount of known degradants + Amount of unknown degradants)
So, here I will convert the equation for better understanding. After each degradation study,
Total % of drug = % drug remained + % known degradants + % unknown degradants