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LC–MS/MS method for the quantification of potential genotoxic impurity 4-phenoxyphenyl-boronic acid in ibrutinib

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Abstract

An effective LC–MS/MS method was developed for the quantification of traces of 4-phenoxyphenyl-boronic acid, a potential genotoxic impurity, in ibrutinib drug. AtlantisT3 Column of dimensions: 150 × 4.6 mm (length x diameter) and particle size: 5.0 μm was used. Gradient elution using ammonium formate buffer (10 mM) and acetonitrile as mobile phase A and B, respectively, was employed. Mass detection was conducted in negative mode with selected ion monitoring (SIM) at m/z 231.02 for 4-phenoxyphenyl-boronic acid. The detection and quantitation limits were established for the said impurity and were found to be 0.134 µg/mL and 0.45 µg/mL, respectively. The developed LC–MS/MS method was validated as per ICH guidelines. The results of validation proved that the developed method was precise, accurate, linear, specific and robust. The method can be effectively used for routine quantification of 4-phenoxyphenyl-boronic acid impurity at trace levels in ibrutinib drug substance.

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Acknowledgements

The authors are thankful to the management of K L University, Guntur, Andhra Pradesh for providing necessary support to the current research work.

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Authors and Affiliations

  1. Department of Chemistry, Koneru Lakshmaiah Education Foundation, Green Fields, Vaddeswaram, Guntur Dt., A.P., 522502, India

    Sumanth Mullangi & Kunta Ravindhranath

  2. Department of Chemistry, BITS-Pilani Hyderabad Campus, Jawaharnagar, Hyderabad, Medchal (Dist), Telangana, 500078, India

    Ravi Kiran Panchakarla

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  1. Sumanth Mullangi
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  2. Kunta Ravindhranath
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  3. Ravi Kiran Panchakarla
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Correspondence to Kunta Ravindhranath.

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Mullangi, S., Ravindhranath, K. & Panchakarla, R.K. LC–MS/MS method for the quantification of potential genotoxic impurity 4-phenoxyphenyl-boronic acid in ibrutinib. J IRAN CHEM SOC 18, 1381–1389 (2021). https://doi.org/10.1007/s13738-020-02118-3

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  • DOI: https://doi.org/10.1007/s13738-020-02118-3

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