Nitrosamines impurities in Losartan Potassium Tablets - Method development and Validation

Revital Rapoport, QA, Managment , Aminolab, Ness Ziona , Israel (revitalr@aminolab.net )

As N-nitrosamines are classified as probable human carcinogens, their presence should be avoided or limited as much as possible.

As a result of the potential toxicity associated with these impurities, the regulatory bodies (FDA , EMEA) require to  take steps to control and limit their presence in pharmaceutical materials.

The presence of nitrosamine impurities has been detected in drug substances and drug products. In 2018, N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA) were detected in some valsartan drug substances and the drug products manufactured from drug substances using specific synthetic routes. This observation triggered extensive synthetic route assessments and development of analytical procedures to quantify these two nitrosamine impurities.

As per current USP general Chapter  1469  (and FDA reccomendations) , the following Nitrosamines are  required to be  determined and monitored:  NDMA, NDEA, NMBA, DIPNA, EIPNA, NDBA .  These impurities have potential and established toxicity with no therapeutic value.

 Aminolab team has focused  in Losartan  Potassium 50 mg   Tablets and  developed an analytical procedure based on USP  recommended  chromatographic conditions using LC-MS/MS (SCIEX 6500). The method was validated : Linearity , LOQ,  Recovery (At LOQ level) and Specificity were demonstrated.  NDBA specificity was challenged due to an interfering peak in the diluent.  

The lecture will describe the challenges we faced during the validation , the way we addressed them, and the final insights gained

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Short Biography of Presenting Author

With over 30 years of analytical and regulatory experience in the pharmaceutical industry,

Revital holds a Ph.D. in Biochemistry from the Hebrew University of Jerusalem.

For many years, she managed QC laboratories at Teva Pharmaceutical Industries across multiple sites,  –

Revital later served as Quality Assurance Director at Teva’s sites in Israel and the United States.

In her roles as Quality Assurance Manager, she was responsible for supervising the production of pharmaceuticals and active pharmaceutical ingredients (APIs).

Approximately  nine  years ago, Revital joined Aminolab, a leading provider of analytical services for the pharmaceutical and medical device industries.

At Aminolab, she managed the chemistry laboratories and later headed the Quality Assurance Department.

Today, Revital serves as Director of Quality Assurance and Regulatory Affairs at Aminolab, supporting pharmaceutical and medical device companies through development, validation, and compliance with international regulatory requirements.

She also lectures and trains professionals in these area