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Nitrosoamines

Piotr_Kujawski

Hello,

We have qTOF 6546. Is there abybody who tried to analised nitrosoamines on qTOF. According to the Agilent application "Determination of Nitrosoamines Using the High Resolution Agilent 6546 LC/Q_TOF"  (link below) it is possible to reach the sensitivity up to
0,1 ppb. I have tried to do this but for e.g NDMA  the sensitivity about 100 ppb is maximum i could reach.For other nitrosamines it is hard to get 10 ppb. 

I did some online reaserch and  found the article: "Nitrosamine Impurities Testing by LC-MS Methods from the United States Pharmacopeia General Chapter <1469>" (link below) where I found that information:

"Our laboratory experienced sensitivity issues with an ultra-modern HRMS detector (Agilent 6546 Q-TOF), and to verify the results different HPLC columns, solvents, and reagents were tested. Chromatographic system suitability criteria could be met, but it was not possible to meet system suitability for overall identification and sensitivity.

 

Do you have any experience with nitrosoamines on qTOF and you could give me some hints about e.g MS tuning? Do tou know how can I contatct with the authors of that aplication to ask for more information?

https://www.agilent.com/cs/library/applications/application-pharmaceuticals-6546-q-tof-5994-1372en-agilent.pdf

https://www.sigmaaldrich.com/PL/pl/technical-documents/technical-article/pharmaceutical-and-biopharmaceutical-manufacturing/small-molecules-analysis-quality-control/quantitative-analysis-of-nitrosamine-impurities

Thank you for nay help,

Best regards, 

Piotr Kujawski

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  • 0

     Thanks for writing to us in this forum.

    I can share my experience about this application note 5994-1372EN. We have used 100 % Water as the sample diluent and 40uL injection volume. This analysis is performed using NItrosamine standard solutions. There are some best practices used in this work:

    I followed below calibration practices before start of the experiment: (follow points 1, 2 and 3)

    Using AJS source ( ESI Calibrant)

     1.TOF Transmission tune to ( 1700 m/z range)

    2.Fragile transmission tune ( m/z 250)

     

    3. Using APCI source ( APCI Calibrant)

    TOF Transmission Tune ( 1700 m/z range)

    OR

     You can do TOF Transmission Calibration as well ( 250m/z range)

     I used High resolution mode while doing tuning and High sensitivity mode while doing calibration.

    In addition to above tuning and calibration steps we need to be careful about other factors as it is most important to keep the baseline noise under control for nitrosamines (specifically NDMA).

    1. Make sure RMSN-4 filters are replaced every 6 months.

    2. I used Activated Carbon Tower with Peak Nitrogen generator to get better quality of nitrogen with lesser hydrocarbon impurities.

    3. Make sure the LCMS water quality is up to the mark as there is big impact of water quality on nitrosamines.

    4. LCMS grade Methanol and formic acid must be used.

    I have one more sample analysis of NDMA in Ranitidine and it worked well too. You can see 5994-1626EN Determination of a Genotoxic NDMA Impurity Using the High-Resolution Agilent 6546 LC/Q-TOF in Ranitidine Drug Substance and Drug Products

    Although I do agree on the fact that Triple quadrupole- based mass specs provide more flexibility in terms of sensitivity to address Nitrosamine challenge.

    Please feel free if you have more questions on this.

Reply
  • 0

     Thanks for writing to us in this forum.

    I can share my experience about this application note 5994-1372EN. We have used 100 % Water as the sample diluent and 40uL injection volume. This analysis is performed using NItrosamine standard solutions. There are some best practices used in this work:

    I followed below calibration practices before start of the experiment: (follow points 1, 2 and 3)

    Using AJS source ( ESI Calibrant)

     1.TOF Transmission tune to ( 1700 m/z range)

    2.Fragile transmission tune ( m/z 250)

     

    3. Using APCI source ( APCI Calibrant)

    TOF Transmission Tune ( 1700 m/z range)

    OR

     You can do TOF Transmission Calibration as well ( 250m/z range)

     I used High resolution mode while doing tuning and High sensitivity mode while doing calibration.

    In addition to above tuning and calibration steps we need to be careful about other factors as it is most important to keep the baseline noise under control for nitrosamines (specifically NDMA).

    1. Make sure RMSN-4 filters are replaced every 6 months.

    2. I used Activated Carbon Tower with Peak Nitrogen generator to get better quality of nitrogen with lesser hydrocarbon impurities.

    3. Make sure the LCMS water quality is up to the mark as there is big impact of water quality on nitrosamines.

    4. LCMS grade Methanol and formic acid must be used.

    I have one more sample analysis of NDMA in Ranitidine and it worked well too. You can see 5994-1626EN Determination of a Genotoxic NDMA Impurity Using the High-Resolution Agilent 6546 LC/Q-TOF in Ranitidine Drug Substance and Drug Products

    Although I do agree on the fact that Triple quadrupole- based mass specs provide more flexibility in terms of sensitivity to address Nitrosamine challenge.

    Please feel free if you have more questions on this.

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