Nitrosamine impurity analysis requires robust and sensitive analytical methods to ensure confidence in the obtained results. The wide Thermo Scientific portfolio is proven to be excellent for nitrosamine analysis, ensuring your exploratory and routine methods are performed as accurately and reliably as possible while maintaining requirements from regulatory bodies worldwide. Our major products for the analysis of nitrosamines include:

  • Liquid, gas, and ion chromatography for robust separation
  • High resolution, accurate mass (HRAM) mass spectrometry for ultimate confidence avoiding false positive results
  • Tandem mass spectrometry, the best tool in routine analysis
  • Single, compliance-ready software solution for all our technology solutions

 

Nitrosamine analysis applications

The use of some common solvents, such as DMF, in the manufacturing process can lead to false-positive results if the interfering compounds cannot be sufficiently separated chromatographically. Orbitrap technology is the gold standard mass spectrometry technique for fast and confident nitrosamine impurity screening, or for piece-of-mind confirmation analysis, which is critical to eliminate false-positive results through interferences. Here are two workflows demonstrating this application:

Routine batch monitoring for specifically identified nitrosamines (as per regulatory recommendations, or by internal risk assessments) requires set methods that may last for years. Tandem MS has long been the method of choice for applications with challenging sensitivity requirements. Combined with proven method robustness, simplicity of use and the ability to easily achieve. Here are two workflows demonstrating this application:

All Thermo Scientific nitrosamine solutions are controlled and operated by Chromeleon CDS software. Built with both the lab and IT in mind, this software delivers superior compliance tools, networking capabilities, instrument control, automation, and data processing. It's a full enterprise solution designed for tracking, accountability, and QA/QC that is incredibly easy to use, with fewer mouse clicks, and more "right-first-time" results. It's also designed to scale globally and provide strong, reliable return on investment.

The use of some common solvents, such as DMF, in the manufacturing process can lead to false-positive results if the interfering compounds cannot be sufficiently separated chromatographically. Orbitrap technology is the gold standard mass spectrometry technique for fast and confident nitrosamine impurity screening, or for piece-of-mind confirmation analysis, which is critical to eliminate false-positive results through interferences. Here are two workflows demonstrating this application:

Routine batch monitoring for specifically identified nitrosamines (as per regulatory recommendations, or by internal risk assessments) requires set methods that may last for years. Tandem MS has long been the method of choice for applications with challenging sensitivity requirements. Combined with proven method robustness, simplicity of use and the ability to easily achieve. Here are two workflows demonstrating this application:

All Thermo Scientific nitrosamine solutions are controlled and operated by Chromeleon CDS software. Built with both the lab and IT in mind, this software delivers superior compliance tools, networking capabilities, instrument control, automation, and data processing. It's a full enterprise solution designed for tracking, accountability, and QA/QC that is incredibly easy to use, with fewer mouse clicks, and more "right-first-time" results. It's also designed to scale globally and provide strong, reliable return on investment.

 

About nitrosamine impurities in drug products

Why is nitrosamine impurity analysis in drugs important?

Nitrosamines, or more correctly N-nitrosoamines, refer to any molecule containing the nitroso functional group. These molecules are of concern because nitrosamine impurities are probable human carcinogens. The unexpected finding of nitrosamine impurities in drugs such as angiotensin II receptor blockers (ARBs), ranitidine, nizatidine, and metformin, has made clear the need for a risk assessment strategy for potential nitrosamines in any pharmaceutical product at risk for their presence. Stringent regulatory guidance’s are not only helping to make drugs safer, but through the method requirements are helping laboratories to identify the appropriate tools needed for accurate and confident analysis.

Regulatory guidance for nitrosamine impurity analysis

 

Thermo Scientific solutions for nitrosamine impurity detection 

Optimal Thermo Scientific solutions for nitrosamine impurity analysis

Nitrosamine AnalysisLC-MSGC-MSIC
  1. Highly confident identification, quantitation, and monitoring
Orbitrap Exploris 120 LC-HRAMOrbitrap Exploris GC-HRAM-
  1. Robust, high throughput routine screening
TSQ Quantis LC-MS/MSTSQ 9000 GC-
  1. Laboratory workflow automation
TriPlus RSHTriPlus RSH-
  1. Single compliance-ready software
Chromeleon CDS SoftwareChromeleon CDS SoftwareChromeleon CDS Software
  1. Nitrite and nitrate assessment
--HPIC system

 

Products for nitrosamine impurity analysis

Advanced LC systems for solving tough analytical challenges

Obtain new benchmarks in accuracy, precision, and sensitivity with the Thermo Scientific Vanquish HPLC and UHPLC systems. With state-of-the-art quaternary or binary high-pressure solvent blending, these ultra-high-performance liquid chromatography systems share all Vanquish values, such as a design focused on uptime, robustness and reliability.

  • Separate more peaks than ever before. The Vanquish system improves specifications on all fronts. It supports higher backpressures, better thermostatting, optimized volumes, better linearity, and more sensitivity.
  • Regain time during your projects. The system improves analysis speed, increases sample capacity and has improved robustness.
  • Operational simplicity of the Vanquish system provided by optimized design and automated features.

Identify and quantify nitrosamine impurities with confidence

Spend less time questioning your results with the unique ability of Thermo Scientific Orbitrap high-resolution, accurate-mass (HRAM) mass spectrometers to provide accurate results and reduce false positives or negatives.

  • Confidently resolve ions of interest from interfering ions with high mass resolution up to 120,000 at m/z 200
  • Maximize your compound coverage with an improved scan rate up to 22 Hz, plus the ability to do both positive and negative mode switching ensures you analyze twice as many analytes in the same sample.
  • Minimize time spent on software training for Thermo Scientific MS users with a common software user interface for data acquisition

Also see: Looking for Thermo Scientific Q Exactive plus Hybrid Quadrupole-Orbitrap Mass Spectrometer?


Develop highly sensitive and robust LC-MS/MS methods for routine, high-throughput testing of nitrosamine impurities

TSQ Quantis Triple Quadrupole Mass Spectrometer

Easily answer critical analytical challenges during targeted quantitation workflows in your laboratory. With its segmented quadrupoles, faster rod drivers, and improved electron multipliers, the Thermo Scientific TSQ Quantis Triple Quadrupole Mass Spectrometer delivers unprecedented robustness with best-in-class sensitivity for everyday use and for every user.

  • Superb sensitivity that generates data for all molecular species, even in complex matrices.
  • Outstanding robustness that enables increased confidence in data while prolonging instrument uptime.
  • Reliability and reproducibility improve data quality for every run and every sample.
  • Simplicity and ease-of-use allow users of all expertise levels to acquire high quality data with improved confidence in results

Robust chromatographic solutions to challenging separations

Get excellent retention and unique selectivity for aromatic and moderately polar analytes.

Advanced GC systems that minimize instrument down time

Simplify analytical workflows with the compact Thermo Scientific Orbitrap Exploris GC mass spectrometer, which brings the versatility of full-scan, high-resolution accurate-mass data to screening and quantitation.

  • Reduce time spent evaluating data and increase confidence with exceptional levels of selectivity, sensitivity, and linear dynamic range
  • Simplify analytical workflows with its versatility of full-scan, high-resolution accurate-mass data to screening and quantitation
  • Deliver results on time and with ease. With intuitive instrument control and method templates, the system is fully accessible to all members of your analytical team

For high-throughput analytical laboratories, the TSQ 9000 GC-MS/MS system provides sensitive, specific quantitation of target compounds.


  • Boost Productivity by analyzing dirtier matrices with minimum clean-up using the system's robust injector technology
  • Lower Your Cost of Ownership with easy-access, tool-free modules
  • Switch Injectors and Detectors in Minutes reducing maintenance downtime dramatically and be back to running samples in minutes & switch to a different workflow or method instantly

See the full GC-MS portfolio ›

Get ahead of the curve by determining nitrite in pharmaceuticals to assess the likelihood of nitrosamine formation before they do.

Dionex IonPac AS19-4µm hydroxide-selective anion-exchange column

Achieve high resolution separations of trace inorganic anions in using the Thermo Scientific Dionex IonPac AS19-4µm hydroxide-selective anion-exchange column. Its high resolution, high capacity and selectivity allow the determination of analytes at low concentrations.

  • Fast, sensitive separations without sacrificing resolution—up to two times faster with Fast IC columns
  • Outstanding resolution using columns with small-diameter particles, thanks to high-pressure capability
  • Continuous operation at up to 5000 psi when configured as a Thermo Scientific Reagent-Free IC (RFIC) system

Minimize environmental contamination and improve laboratory productivity by automating the sample preparation for nitrosamine impurity analysis

TriPlus RSH Autosampler

Sample preparation steps, which can account for more than 60% of the time spent on chromatographic analysis, generally include extraction, clean-up, dilution, standard addition, derivatization, mixing and heating. The Thermo Scientific TriPlus RSH Autosampler can eliminate the sample preparation bottleneck for both online automation for GC-MS, and off-line automation for GC-MS and LC-MS.

  • Error-free sample handling
  • Reduced manual steps helping to eliminate environmental contamination
  • Stand-alone bench top preparation for LC-MS and GC-MS or online GC-MS with compliance-ready control

Compliance-ready operation and data processing for every Thermo Scientific nitrosamine solution, enabling confidence in data generation and result reporting

Chromeleon CDS software

Built with both the lab and IT in mind, this software delivers superior compliance tools, networking capabilities, instrument control, automation, data processing, and much more. It's a full enterprise solution designed for tracking, accountability, and QA/QC that is incredibly easy to use, with fewer mouse clicks, and more "right-first-time" results. It is also designed to scale globally and provide strong, reliable return on investment.

  • Improved lab productivity helps you do more with less and realize significant productivity gains
  • Right first-time results and reduced out-of-specification results, even for non-expert users
  • Easier to achieve, maintain, and demonstrate compliance, making it easier than ever to keep up with ever-evolving standards and regulations

Single compliance-ready solution for all analytical solution for nitrosamine impurity analysis.

All Thermo Scientific systems for nitrosamine impurity analysis can be operated by Chromeleon CDS software, giving confidence in results which ever direction your laboratory takes.

Nitrite impurities are found in a range of commonly used excipients, which may lead to nitrosamine impurities forming in drug products during the drug product manufacturing process and shelf-life storage. Therefore, it is important to limit the nitrite and amine levels in drug substances and drug products. Reagent-Free™ (RFIC™) ion chromatography coupled with high capacity IC column allows for assessment and quantitation of nitrite levels even in the presence of high concentration counterions such as chloride.

Download: Determination of nitrite in pharmaceuticals ›

 

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