👨‍💻 Determination of nitrite and nitrate in povidone by ion chromatography as part of nitrosamine risk assessment in excipients

Povidone (polyvinylpyrrolidone, PVP) is a commonly used excipient in the formulation of different pharmaceutical dosage forms. It serves as a suspending and dispersing agent, as well as a binding, granulating, and coating agent for tablets.
Nitrites present as impurities in excipients are the primary source of nitrosating agents that can lead to the formation of nitrosamines1. In this process, the rate-limiting factor is usually the trace levels of nitrite, rather than the more abundant secondary amine. This analytical note describes
a selective and sensitive ion chromatography procedure for determining nitrite and nitrate levels in povidone. The method utilizes anion exchange separation coupled with conductivity detection.

Limit of Quantitation (LOQ): 0.2 ÎĽg/g for nitrite and
1.2 ÎĽg/g for nitrate with respect to 25 mg/mL sample
concentration
Validated Range: 0.2 ÎĽg/g - 20 ÎĽg/g for nitrite and 1.2
ÎĽg/g - 40 ÎĽg/g for nitrate with respect to 25 mg/mL sample
concentration.
Precision: %Relative standard deviation (RSD) of nitrite
and nitrate of the 6 recoveries at LOQ levels were less than
20%
Accuracy: %Recovery for nitrite at 0.2 ÎĽg/g, 4 ÎĽg/g, 20
ÎĽg/g and nitrate at 1.2 ÎĽg/g, 8 ÎĽg/g, 40 ÎĽg/g were within
100 ± 30.0%

@mayank.bhanti @Mrunal @SureshP

USP Application Note:
Nitrite and nitrate in povidone_AppNote v03.pdf (1.8 MB)

Disclaimer

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Dear Naiffer,
thank you for sahring this.
It is very interesting that USP provides an official method of determination of nitrites in an excipient with very low LoQs.
Do you know if there is any relative method(s) also for other critical excipients, as MCC, lactose, manitol etc?
Furthermore, i am wondering of this method for povidones could be applied also for other excipients.
best regards
Christos

@chrischar I want to clarify that this is NOT an official USP method. Our labs developed it in support of the ongoing analytical efforts by stakeholders. I don’t see why not it could be extended to other excipients, of course with the necessary evaluation/validation. I will let @mayank.bhanti answer specifically, because his lab led all the development.

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thanks a lot for the clarification Naiffer!!

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