Azido impurities by APCI-LC-MS

Confirmatory Testing & Analytical Challenges
1

Hello everyone.
I have been developing an analytical procedure of AZBT in sartan drugs by APCI-LC-MS and have found that when using high concentration of API (~ 20mg/ml), the recovery is unexpectedly high, about 150%, in different level. This phenomena correlated with the concentration of API in sample solution. The AZBT content in API <LOQ by the same procedure. Can anyone help me solve this problem? Thank you very much.

2

Check for MS2 scan at the analyte elution time range and verify with the MS2 scan for 100 % target and recovery samples… along with blank/standard/sample matrix…

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@minhluan , the connection between the increased API concentration and higher recovery rates, along with the observation that AZBT content in the API is below the LOQ using the same method, raises certain points for consideration:

  1. Sample Dilution: Investigating the effects of diluting the sample to levels that match expected recoveries can help determine if the elevated recovery is linked to matrix effects (as indicated below).

  2. Interferences and Co-elution: a careful examination of possible interferences or overlapping of AZBT with other substances, influenced by the elevated API concentration, is necessary. These interactions might be causing the higher recovery rates that have been observed.

  3. Ionization Mechanisms: The influence of varying API concentrations on ionization dynamics, especially in APCI (mass-dependent ionization process), can be instrumental in understanding this observation.

  4. Matrix Effects: The potential influence of the matrix on ionization efficiency, chromatographic separation, and response factors should be evaluated.

I eagerly anticipate your input

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Hai lucas
Point 2 is " Interferences and Co-elution : a careful examination of possible interferences or overlapping of AZBT with other substances, influenced by the elevated API concentration, is necessary. These interactions might be causing the higher recovery rates that have been observed " is important

This can be identified with MS 2 scan for your method with Blank/Sample/Spiked sample

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Dear Lucas! Dear Sagar!
Thank you for treating me so kind! I really appreciate your advice and I will investigate them, respectively.

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@minhluan Don’t forget to report back the conclusions… it will be great for all the participants to see the outcome of our discussion here. Thanks

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7

In this situation, I decided to switch to negative ionization instead of positive mode and the issue seems to be solved.

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When looking at different ionization polarities, negative mode ionization is generally less affected by ion suppression. This is because it’s more specific.

In positive polarity, many interfering substances can create positively charged ions, competing with the target analyte for charge.

On the other hand, in negative polarity, fewer compounds generate negative ions, resulting in a lower level of ion suppression.

Please refer to: Overview, consequences, and strategies for overcoming matrix effects in LC-MS analysis: a critical review

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We can get more specificity but less intensity result. Thank you very much!