Nitrite content in hydroxypropyl methylcellulose

IFF have just published a promo giving details of the nitrite content of a range of their HPMC products. As usual the variability is quite high ranging for example for K200M from 82 - 286 ppb.

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I saw this yesterday as well.
Some grades seemed to be claiming very low levels.
Was interesting that they published their method for achieving the analysis as well - I think people have struggled with sample prep for HMPC at times, possibly a way forward.

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Thanks both! @MarkS can you share the document of the methodology? Or provide the link? Thx

Hi @Naiffer_Host.

Please see attached for a brief description of the method, I think there may have been more in another document, I’ll try and find it again.



In a recent (May 2023) EMA QWP paper, EMA drew attention to formaldehyde catalysed nitrosation at pH > 6, pointing as well to the literature identifying a risk for formaldehyde contamination in excipients like hydroxypropyl cellulose and some others (levels ca. 10 ppm). Overall concluding that “It is not yet clear whether the contamination of excipients with formaldehyde is a real risk factor in the generation of N-nitrosamines during drug product manufacture although at the moment, there is no robust scientific data to exclude this possibility.”
I’m wondering if more attention will be given to testing less obvious nitrosamine risk factors in excipients in the future, now that the nitrite contamination is being more and more studied (and controlled) by excipient suppliers as well, as shown by this nice contribution on nitrite in HMPC.

Formation of N-Nitrosamine Drug Substance Related Impurities in Medicines: A Regulatory Perspective on Risk Factors and Mitigation Strategies

Răzvan C. Cioc, Ciarán Joyce, Monika Mayr, and Robert N. Bream
Organic Process Research & Development 2023 27 (10), 1736-1750
DOI: 10.1021/acs.oprd.3c00153


I’m keeping an eye out for that pesky formaldehyde, as well as nitrite these days!

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