When we are using L-cysteine as nitrite scavenging, do we need to have the assay test of L-cysteine in finish product as a part of specification? if yes what should be the limit?
@chirag … do you have bit more information or context to your inquiry? That will help the community digest better your question. Thanks
Hi Naiffer, i have added L-Cysteine in one of my formulation to control nitrosamine impurity and found positive results, now my question is do i need to monitor the amount of L-Cysteine present in formulation on a routine basis as a part of stability study?
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Hi Chirag,
I do not know in which countries is authorized our product; I can only answer for the European countries.
All the guideline on excipients were written well before the nitrosamines issue, so there is no clear indication on nitrite scavengers.
However, nearly all nitrite scavengers (like L-Cysteine) are antioxidants; therefore, according to the EMA guideline:
in my opinion the answer is yes, you should include L-Cysteine identity and assay in your specifications.
Regarding the limits, the only (vague) indication is reported in an old EMA guideline:
Specifications and control tests on the finished product
For chemical preservatives (antioxidants), the lower limit may be considerably lower than 90% during the shelf life, because of the preferential degradation of these agents.
Summarizing, you should define your lower limit according to your stability data. Even 70% (or less) at the end of shelf-life may be acceptable, provided that this concentration is still effective to inhibit the formation of nitrosamines.
I hope I have clarified your doubts.
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Dear Chirag,
as the addition of L-cysteine is a part of a mitigation risk plan, first of all you should identify the minimum quantity in which this is effective.
As this reagent will react with the nitrites in the formulation, its quantity will decreased during time, so you should record it through stability in order to ensure that its quantity will be always over the minimum level you have identify.
So, i beleive that you should add this in your specifications.
In addition and independently of nitrosamine cases, the antioxidants are included in the specs when they are present in the formulation.
Christos
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thanks for the valuable suggestions.
I really had not thought of this at all but concur. At the end of the day, it should be treated really similarly to a preservative. Both are put in at a specific amount and expected to be consumed over time.
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