Nitrosamines

Based on isotopically labeled standards, our customizable in-house detection methods are available immediately.
We provide unparalleled risk evaluations which can identify active substances and finished products at risk of N-nitrosamine formation or (cross)-contamination with these impurities.

Overview

Detection of N-Nitroso-N,N-dimethylamine (NDMA) in 2018 in Valsartan, a medicine for blood pressure control, followed by similar observations in Losartan-, Ranitidine- and Metformin- containing products led to temporarily limited availability of medications around the globe and initiated massive risk-assessment campaign for all human medicines containing chemically synthesized APIs.

The scope of the risk-assessment campaign and multiple possible root causes of the contamination create imminent need of robust and reliable determination of Nitrosamines content in various types of matrices. Quinta-Analytica decided to contribute to patients’ safety and to support the pharmaceutical industry by developing versatile proprietary ULPC/MS/MS method for quantitative determination of Nitrosamines under full GMP conditions.

The method is based on isotopically labeled internal standard and was inspired by the methods published by the regulatory bodies. Slight modification of its parameters and/or the sample preparation allows the customization to the specific matrix. The method has been successfully applied to APIs, solid dosage forms, solutions for infusion, oral solutions, semi-finished products or excipients.

Our experience goes far beyond N-Nitroso-N,N-dimethylamine (NDMA) determination and, till the date, we have practical experience with eight Nitrosamines which confirms the versatility of the method:

  • N-Nitroso-N,N-dimethylamine (NDMA)
  • N-Nitroso-N,N-diethylamine (NDEA)
  • N-Nitroso-N-methylbutyric acid (NMBA)
  • N-Nitroso-N,N-ethylisopropylamine (NEIPA)
  • N-Nitroso-N,N-diisopropylamine (NDIPA)
  • N-Nitroso-N,N-ethylmethyamine (NEMA)
  • N-Nitroso-N,N-dipropylamine (NDPA)
  • N-Nitroso-N,N-dibutylamine (NDBA)

The solution provided by Quinta-Analytica has proven to deliver the sensitivity required by the interim limits set upon maximum daily intake but is ready for expected strengthening of the limits (down to 30 ppb and even lower). Limit tests will be implemented after the final specification and methodologies will be codified by the regulatory bodies..

Current range of API applications validated by Quinta-Analytica:

Sartans

Valsartan

Valsartan disodium

Losartan Potassium

Losartan Free Base

Candesartan

0.02 – 2

0.02

0.2 – 20

0.2

0.02

0.03 – 3.33

0.03

0.02*

0.02*

0.2*

Others

Active Pharmaceutical Ingredients

Nitrosamine

LOQ (ppm)

Method range (ppm)

Ranitidine HCl

Other APIs

NDMA

NDMA

NDEA

NMBA

NEIPA

NEIPA

NDIPA

NDIPA

NEMA

NDPA

NDBA

NDBA

NDMA

NDEA

NDEA

NMBA

NMBA

NDMA

NDEA

NDMA

NDEA

NDMA

NDMA

0.2 – 10

0.2

0.02 – 2

0.02

0.2 – 20

0.2

0.02 – 2

0.02

0.02 – 1

0.02

0.02 – 1

0.2 – 10

0.02 – 1

0.2 – 20

0.2

0.02 – 1

0.02

0.2 – 10

0.2

0.2 – 20

validations in progress routinely

0.2

0.02

0.02

0.02

0.02

0.02

0.02

0.02 – 1

0.02 – 1

0.02 – 1

0.02 – 1

0.02 – 1

0.02 – 1

0.02 – 1

* Validation is still running and LOQ will be declared soon

There is a dedicated cross-functional team dedicated to the Nitrosamines project which assures tailoring the project scope to the customer’s needs and secures delivery of the results within the agreed timeframe. Based on the requirement, we provide either indicative screening results or validated GMP results. The standard scope of the validation program is: SST, Selectivity, LOQ, Linearity, Precision and intermediate precision (n=12), Accuracy, Range, Robustness and Stability.

Examples of typical lead times:

  • Development of the custom limit test: 2 weeks
  • Development of the custom quantitative method: 3 weeks
  • cGMP validation of the method for one product incl. reporting: between 2.5 and 4 weeks (depending on number of impurities to be reported)
  • Screening of the sample using already routine method: 5-10 working days with throughput of 50 samples per day
  • Quick pre-screening of the samples using in-house general method: within 2 weeks (number of the impurities to be reported is product specific)

Get in touch with one of our Nitrosamine experts today, or use the contact information for our commercial team below, and see how we can create the perfect solution for you.

Additional Services

API SOlution

Broad portfolio of active ingredients from reliable, established manufacturers, guaranteed by our expertise.

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Nitrosamines

Based on isotopically labeled standards, our customizable in-house detection methods are available immediately.

More Info →

REGULATORY AFFAIRS

Expertise in helping to compile dossiers and drug registration processes.

More Info →

MONITORING OF STUDIES

Oversight of participant health and correctness of treatments during clinical studies.

PHARMACOVIGILANCE

Monitoring of daily routine to detect unrecognized adverse events, plus assess and ensure drug safety.

MODULE 3 AUDIT

Thorough dossier M3 data audit to ensure consistency and compliance with regulatory requirements.

GENERICS IN RUSSIA

Via our partnering CRO in Russia we can help you to perform clinical trials to apply for Russian MA.

IMPD COMPILATION

As an EU based company we are well-placed to help create & develop your IMPD.

AND MUCH MORE

It's not an exhaustive list so if you don't see what you need, contact us.

Questions?

Our Commercial Sales team is happy to help: sales@quinta.cz

Jiří Raška

Chief Commercial
Officer

David Dvořák

Business Manager
& Scientific Advisor

Pavel Pihera

Business Manager
& API Sourcing Manager
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Questions?

Please use the contact details or form below.

quinta@quinta.cz

+420 242 454 311

For general and business contact only. To register as a volunteer for clinical studies (CZ nationals only) or speak with our clinical department, please visit here.

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