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:
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 Solution Guide
All the tools you need for nitrosamine impurity analysis
Nitrosamine analysis applications
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
Stay up to date on what regulatory agencies are saying about nitrosamines impurities and learn more about what they are asking the pharmaceutical industry to do to prevent unacceptable levels.
Thermo Scientific solutions for nitrosamine impurity detection
Optimal Thermo Scientific solutions for nitrosamine impurity analysis
| Nitrosamine Analysis | LC-MS | GC-MS | IC |
|---|---|---|---|
| Orbitrap Exploris 120 LC-HRAM | Orbitrap Exploris GC-HRAM | - |
| TSQ Quantis LC-MS/MS | TSQ 9610 GC-MS | - |
| TriPlus RSH SMART | TriPlus RSH SMART | - |
| Chromeleon CDS Software | Chromeleon CDS Software | Chromeleon CDS Software |
| - | - | 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.
Vanquish Flex UHPLC Systems
Succeed with flexibility. Vanquish Flex UHPLC systems excel from method development to routine analyses. With binary and quaternary pump options, the Vanquish Flex UHPLC systems offer outstanding performance for LC and LC-MS based nitrosamine workflows.
Vanquish Core HPLC System
Eliminate disruptions to your routine analytical work with the Vanquish Core HPLC system. Switching to Vanquish Core is simple and seamless. A full suite of method transfer tools, including tune-able gradient delay volume, makes adoption easy. Like all members of our Vanquish product line, Vanquish Core HPLC systems offer hardware precision and simplicity of operation. Ideal for routine nitrosamine impurity analysis.
- 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.
Orbitrap Exploris 120 Mass Spectrometer
The proven Orbitrap technology in the Thermo Scientific Orbitrap Exploris 120 mass spectrometer accelerates your route to qualitative and quantitative confidence for both method development and everyday testing purposes. With its unique ability to provide consistently accurate data and a design made for operational simplicity, it sets the new standard in instrument productivity and ruggedness.
- 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.
Hypersil GOLD Phenyl Reversed Phase HPLC Column
Thermo Scientific Hypersil GOLD Phenyl RP HPLC columns utilizes a butyl (C4) linker in the phenyl bonded phase allows for superior alignment of the phenyl ring with aromatic molecules, while providing the stationary phase with moderate hydrophobicity, making it ideal for the separation of analyte mixtures with varying polarity and aromaticity.
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.
Thermo Scientific Orbitrap Exploris GC Mass Spectrometer
Reduce time spent evaluating data and increase confidence with exceptional levels of selectivity, sensitivity, and linear dynamic range that come together to deliver accurate results, in all sample matrices. Full-scan, high-resolution MS data allows multipoint compound identification with spectral matching, isotope patterns, retention indices, and elemental compositions to reduce time to results
- 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 9610 GC-MS/MS system provides sensitive, specific quantitation of target compounds.
Thermo Scientific TSQ 9610 GC-MS/MS
Delivering attogram-level sensitivity and best-in-class selected reaction monitoring (SRM) performance, the TSQ 9610 GC-MS/MS system consistently meets required detection limits as you run samples. Choose the rugged Thermo Scientific ExtractaBrite ion source or the ultra-sensitive, ultra-robust Thermo Scientific Advanced Electron Ionization (AEI) ion source, depending on your sensitivity needs.
- 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
Get ahead of the curve by determining nitrite in pharmaceuticals to assess the likelihood of nitrosamine formation before they do.
ICS-6000 Capillary HPIC
Obtain high performance, convenience, and flexibility by using our top-of-the-line IC platform optimized for capillary flow rates. The Thermo Scientific Dionex ICS-6000 Capillary HPIC System enables you to scale down column size, injection volumes, and flow rates by a factor of 25 to 100. With a capillary configuration, your system is always ready and able to run samples 24/7 with minimal calibration and equilibration time.
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 SMART 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 SMART 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.
Resources
Webinars
Addressing Analytical Challenges of Nitrosamine
Solutions for Nitrosamine Analysis by GC-MS
Complete Nitrosamine Analysis Webinar Series 2021
Brochures
Vanquish Core HPLC System
Orbitrap Exploris 120 LC-HRAM
TSQ Quantis LC-MS-MS
Orbitrap Exploris GC-MS
Additional brochures
Application notes
Highly sensitive method for the determination of 12 nitrosamine impurities in multiple ARBs, the class of sartan drug formulations
Reliable quantitation of 11 Nitrosamine impurities in Metformin
LC-MS/MS – Nitrosamine impurities in Metformin
GC-MS/MS Nitrosamine impurities in Valsartan
GC-HRAM Nitrosamine impurities in Metformin.
LC-HRAM-MS method for simultaneous quantitation of sixteen nitrosamines in multiple drug products
Additional Resources
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