Where did it start?

Nitrosamines are a large group of N-nitroso compounds that share a common functional N-N=O group. They are produced by a chemical reaction between a nitrosating agent and a secondary or tertiary amine. Back in 2018, nitrosamines suddenly found themselves in the spotlight when they were unexpectedly detected in medications for high blood pressure. Since then, they have been found in several other prescription medications, including those for heartburn, acid reflux and diabetes, resulting in manufacturers recalling some common medications.

Here are a few examples of how SCIEX solutions can help support the development and manufacturing of pharmaceutical drugs with these analytes.

Identification and sensitive quantitation of N-nitroso betahistine (NNBH) impurity in betahistine (BH) active pharmaceutical ingredient

BH is an H1 receptor agonist and an H3 receptor antagonist, which can be chemically synthesized. The structure of BH includes a secondary amine, which is more reactive in the formation of nitrosamines than the tertiary amines. The regulation has amended the maximum permissible daily intake limit for NNBH as 18 ng/day which is equivalent to a maximum daily dose of 48 mg/day. Given that BH has a maximum daily dose of 48 mg/day, a nitrosamine limit of 0.375 ng/mg is required to be quantified in the API. This technical note presents a reliable workflow for the identification and sensitive quantitation of NNBH in BH API below the calculated specification limit using the QTRAP 4500 system.

Read more, here >

Identification and sensitive quantitation of N-nitroso N-desmethyl orphenadrine (NNDO) impurity in orphenadrine citrate API

Orphenadrine citrate (OC) is an anticholinergic drug of the etholamine antihistamine class, which can be chemically synthesized. OC has a secondary amine in the structure, which is more reactive in the formation of nitrosamines than the tertiary amines. The regulation has amended the maximum permissible daily intake limit for NNDO as 18 ng/day which applies to a maximum daily dose of 200 mg/day. Given that OC has a maximum daily dose of 200 mg/day, a nitrosamine limit of 90 pg/mg is required to be quantified in the API.

This technical note presents a reliable workflow for the identification and sensitive quantitation of NNDO in OC API below the calculated specification limit using the QTRAP 7500 system.

Read more, here>

How to ensure compliance for your biotherapeutics from development through to quality control (QC)

SCIEX OS software is a GxP compliance-ready solution integrating data acquisition with the SCIEX time-of-flight mass spectrometers and the SCIEX triple quadrupole systems. Learning just one software allows even less experienced MS users to be trained rapidly to acquire and convert raw MS data into product quality attribute results. The software offers ample flexibility in defining security settings by allowing the creation of customized user roles with different levels of access to the software’s control. Comprehensive and easily readable audit trails guarantee traceability and data integrity.

Read more, here >

If you are looking for more information about analyzing nitrosamine impurities by LC-MS, discover our Spotlight on series in which we highlight a different challenging molecule or class of compounds and related LC-MS solutions. Find out more about the nitrosamines featured here.