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Identification and Characterization of a New Process Related Impurity in Terbutaline Sulfate by Accurate-Mass Q-TOF LC/MS/MS and NMR

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Abstract

An unknown impurity at the level of 0.62% was observed during routine analysis of Terbutaline Sulfate drug substance. The impurity was isolated using preparative HPLC and the impurity was comprehensively characterized with the help of spectroscopic studies. The characterization tools include accurate mass quadrupole time-of-flight (Q-TOF) LC–MS/MS and NMR (1H, 13C, DEPT). Based on the obtained data, the impurity was identified as N-tert-Butyl-N-[2-(3, 5-dihydroxyphenyl)-2-hydroxy-ethyl] acetamide (labeled as Impurity-1a). The existing HPLC method was subsequently validated for determination of this new impurity according to ICH guidelines. In order to understand the formation and apply necessary controls over the process a probable mechanism for the formation of same is discussed in detail.

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Acknowledgements

The authors are thankful to the management of Deepta Laboratories for providing samples, to Mr. Rajeev Chadar, Mr. Vasantha K. Kadambar and Mr. Arun Bhardwaj for their co-operation in carrying out this work.

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Authors and Affiliations

  1. Ipca Laboratories Ltd., Vadodara, 391445, India

    Santosh Patil, Gajanan Kantikar & Poonam Koppula

  2. School of Sciences, GSFC University, Vadodara, Gujarat, 391750, India

    Santhosh Koppula

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  1. Santosh Patil
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  2. Gajanan Kantikar
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Correspondence to Santhosh Koppula.

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Patil, S., Kantikar, G., Koppula, S. et al. Identification and Characterization of a New Process Related Impurity in Terbutaline Sulfate by Accurate-Mass Q-TOF LC/MS/MS and NMR. Chromatographia 84, 381–391 (2021). https://doi.org/10.1007/s10337-021-04021-2

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  • DOI: https://doi.org/10.1007/s10337-021-04021-2

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