Mass balance for forced degrdation studies

GOOD VALIDATION PRACTICE (cGVP) LABORATORY, METHOD AND ANALYTICAL VALIDATION
1

Dear sir how to establish mass balance for forced degrdation studies in HPLC method validation.I want clear explanation with
examples.
Thank u

2

Mass balance correlates the measured loss of a drug (API) to the measured increase in the amount of degradation products. In mass balance calculations, the amount of drug (remaining in stresses sample) is determined from an assay by HPLC method, and the increase in degradation products is determined by related substances by HPLC method.

Then, actual degradation % = quantity of measured impurity (degradant) (%, w/w) x (A/B)
Where, A = Mol. Wt of API and B = Mol. Wt. of impurity

Ex.: Let us consider Paracetamol. Its molecular weight is 151.2. After stress studies, it is found that 2.5% of 3-chloro impurity (molecular weight 185.6) is formed.

Then actual degradation % = 2.5 x (151.2/185.6) = 2.04
So, the assay result (amount of non degraded drug) is 100-2.04 = 97.96, but not 100-2.5 = 97.5

3

Perform sressed samples(Solution stress and Solid Stress) and non stress sample by HPLC decradation products (RC) method.

Calculate,

  1. Calculate Assay of active remaining in both stressed and non stressed samples by RC method against reference standard.
    2)Calculate the total % found in both the samples.

Mass Balance =Total % found in stressed samples/ Total % found in non- stressed SamplesX100

Total % Found= % Active Remaining+% of Known RC’s + % of unknown

Regards,
abhaskar

4

Hi,

Refer the Following article

http://stabilitystudies.blogspot.in/2011/08/mass-balance-ratio.html

N.Srikanth

5

Dear sir please let me know what is RC Method

Regards
Chandra sekhar

6

sir
i am trying to open the following article
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. but i am getting This blog is open to invited readers only message .
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i already created login id & password also, but why it is happening like this , please help me to go through that article.

7

I have seen the literature: Stability Indicating assay method.

Is there any guide speaking stability indicating Related substances method.

Regards,
Bujji Kanchi.

8

Stability Indicating Method
A stability indicating method (SIM) is a quantitative test method that can detect possible degradants and impurities of drug substance (API) and drug products, normally using High Performance Liquid Chromatography. Stability information is needed for regulatory submissions such as IND (Investigational New Drug Application) and NDA (New Drug Applications) and to set expiration dates for the API or drug product.
Before performing stability studies, a stability indicating method is necessary so that any possible degradants generated during storage conditions (such as 5°C, 25°C/60%RH and 40°C/75%RH) can be separated, detected, and quantitated. SIM is useful for checking the quality of the drug substance or product that changes over time in response to environmental factors such as temperature, humidity and light. It establishes the storage and packaging conditions for the drug product.

The method should be sensitive to the reportable impurity level. LOQ (Limit of quantiation), which is typically 0.05% of Label Claim, should be established in the method, and the method should be linear from LOQ to typically up to 150% of the nominal standard (std) concentration.

Stability indicating methods are needed for:

  1. Stability studies
  2. API release
  3. Drug product release
  4. Toxicology dosing solutions
  5. Excipient compatibility and preformulation
  6. Packaging studies
  7. Line extension

Cases where stability indicating methods are not needed:

  1. In process controls
  2. Titration
  3. Inorganics
  4. Limit tests
  5. Cleaning validation
9

[quote=snagabiru]Hi,

Refer the Following article

http://stabilitystudies.blogspot.in/2011/08/mass-balance-ratio.html

N.Srikanth

[/quote]

Dear sir,

I am trying to open this article but it requires invitation from you. Can you send invitation for the same.

Thanks & Regards,
Srinivas