Nitrosamines in Active Ingredients

News & Events In June 2018, regulatory authorities raised alarms on the presence of one Nitrosamine in a widely used drug product. As the extent of this issue has snowballed in recent months, Solvias has increased their capabilities in that area. The first incidence of this group concerned a single Nitrosamine in Valsartan, an angiotensin II...

News & Events

In June 2018, regulatory authorities raised alarms on the presence of one Nitrosamine in a widely used drug product. As the extent of this issue has snowballed in recent months, Solvias has increased their capabilities in that area.

The first incidence of this group concerned a single Nitrosamine in Valsartan, an angiotensin II receptor blocker (ARB). Since then, additional Nitrosamines have been found in other ARBs ("Sartans") as well as other active ingredients. This has led to recall of drug products containing Ranitidine, a histamine H2 receptor blocker, in the US and a review by the EMA. Additionally, the EMA has urged manufacturers to test drugs containing pioglitazone, an insulin sensitizer. Recalls and further reviews are being carried out by national authorities well, e. g. Canada, Switzerland and Singapore.

While the use of certain solvents and synthetically steps have been identified as probable causes, the reasons for Nitrosamines appearing in a diverse array of drug products remain to be fully understood. However, the carcinogenic potential of Nitrosamines demands swift and comprehensive action. The overall goal is to reduce the cancer due to the intake of necessary drugs products below an acceptable level.

Several methods have been published by the FDA to cover NDMA and NDEA in different sartans. The EMA has indicated the extension of measures to include more nitrosamines. Other regulatory authorities have enacted their own measures and published analytical methods on their own, e. g. Canada, Switzerland and Singapore.

Nitrosamines analysis poses a double challenge in that ultra-low levels of impurities need to be quantified in challenging and diverse matrices. These all have to be ultimately validated to conform with GMP requirements.

Solvias offers a comprehensive portfolio of analytical techniques, with dedicated teams specialized in Extractables & Leachables and Genotoxic Impurities. Both teams consist of experts in their field, drawing on years of expertise in the field. Combined with state-of-the art analytical equipment such as Orbitrap LC-MS systems and GC-MS, capabilities are up to the task. Currently, all major Nitrosamines can be reliably quantified, like:

  • N-nitrosodimethylamine (NDMA)
  • N‑nitrosodiethylamine (NDEA)
  • N-nitrosoethylisopropylamine (EIPNA)
  • N-nitrosodiisopropylamine (DIPNA)
  • N-nitroso-N-methylamino butyric acid (NMBA).

Solvias has been particularly involved in Nitrosamine analysis since very beginning and can offer guidance on the best way tackle this challenging analytical and regulatory topic.

What is your current need in that area? Contact us for guidance on the best way to approach this pressing topic and discussion of your specific requirements.

back to overview

Source: www.solvias.com