N-nitroso-Furosemide

Confirmatory Testing & Analytical Challenges
1

Hi everyone,

The laboratory we commissioned the development of a method for determining N-nitroso-furosemide content in a Drug Product is encountering many difficulties and, even now, after more than a year of work, has not been able to finalize the method. Has anyone found themselves in the same situation, or have you been able to finalize the method for N-nitroso-furosemide determination?

2

Furosemide was kind of a challenge. Some quick tips:

Don’t use water in sample preparation.

Depending on the nitrite content of each product (which varies from batch to batch), we observed quite dramatic in vitro formation.

Using scavengers resulted in decomposition of the nitrosamine.

LC-MS was easy, and the method was robust over a wide range.

What are you struggling with?

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I found a paper regarding the NDSRI analysis of Furosemide. I hope you find it helpful.

Ultra-Sensitive and Green LC–MS/MS Method for Trace-Level Determination of Nitrosamine Drug Substance-Related Impurities in the Anti-Diuretic Drug Furosemide

https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/epdf/10.1002/sscp.70217

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Bahsettiğiniz makale çok işe yarar gibi görünüyor fakat ücretli bir site olduğu ve işyerinden bir hesap açmam mümkün olmadığı için erişemiyorum. Makaleye ulaşabilen ve deneyen oldu mu? Bana yardımcı olabilir misiniz?

7

What type of standard do you use?

So far, only the salt form (the sodium salt) has been stable in our tests. The free acid standard degraded rapidly and showed a similar m/z, but the chlorine isotope ratio was incorrect, indicating the presence of two chlorine atoms instead of one.

This suggests that some kind of intermolecular reaction was occurring in the free acid standard.