Determination mass balance ratio in stress studies

1.0 OBJECTIVE                    

To provide the procedure for the determination mass balance ratio in stress studies

2.0 SCOPE

This procedure is Applicable to the determination of mass balance ratio in stress  studies

3.0 RESPONSIBILITY 

3.1 QC-Chemist 

4.0 ACCOUNTABILITY         

4.1 Executive – Quality control

4.2 Head – Quality control

5.0 PROCEDURE     

5.1 Mass balance correlates the measured loss of a parent drug to the measured increase in the amount of degradation products. It is a good quality control check on analytical methods to show that all degradation products are adequately detected and do not interfere with quantitation of the parent drug (i.e., stability-indicating methods).

5.2 How much 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.

 5.3 How Mass Balance Calculated?

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.

 5.4 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

5.5 Factors effecting the Mass balance Ratio 

5.5.1Relative response factors play an important role to calculate the exact mass balance.

5.5.2 The molecular weight of Drugs and the molecular weight of the degradant formed plays an important role to calculate the exact mass balance.

5.5.3  Poor recovery of Parent or Drug product 

5.5.4 Chromatographic issues in drug and degradants 

6.0 ANNEXURES

Nil