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High-Throughput GC-FID Method for the Determination of Residual Solvents in Early-Phase Drug Discovery Samples

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A Correction to this article was published on 29 June 2022

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Abstract

In drug discovery environment, determination of residual solvents is indispensable and requires rapid analysis covering a maximum number of commonly used solvents especially with small quantity of sample and short run times. As of now, the reported methods require a large amount of sample (~ 50 to 200 mg) and long run times, which is not feasible in the drug discovery environment. Hence, in the present work, we have reported a high-throughput and sensitive GC-FID method by using less amount of sample (5 mg) within 9 min of total run time on DB-624 column with helium as carrier gas. This method is capable of resolving 40 residual solvents and particularly separated nine critical pairs which were not resolved well in earlier reports. As a part of method development, we have evaluated and optimized the relevant chromatographic parameters to improve the separation efficiency and sensitivity. The data acquisition rate of the FID detector was evaluated at different scan rates and significant improvement in the peak response of the analytes was found at 5 Hz by 100-fold. This developed method was validated as per ICH Q2 (R1) and is more advantageous in the drug discovery environment, as it provides high sensitivity and low turnaround time (TAT).

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Acknowledgements

The authors would like to thank Bristol Myers Squibb and Syngene International Ltd for providing infrastructure support to do this work. Also, the authors thank Dr. Ramaprasad Ganni, Agilent Technologies, Bangalore Urban, Karnataka, India, for providing technical support.

Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

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Authors and Affiliations

  1. Discovery Analytical Sciences, Biocon Bristol Myers Squibb Research and Development Center (BBRC), Syngene International Ltd, Biocon Park, Plot No. 2 and 3, Bommasandra IV Phase, Jigani Link Road, Bangalore, 560099, India

    Ruba A. Arulraj, Raju Gajjela, Siddheshwar Kisan Chauthe & Muralidhararao Bagadi

  2. Small Molecule Drug Discovery, Bristol Myers Squibb Research and Development, P.O. Box 5400, Princeton, NJ, 08543-4000, USA

    Arvind Mathur

Authors
  1. Ruba A. Arulraj
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  2. Raju Gajjela
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  3. Siddheshwar Kisan Chauthe
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  4. Muralidhararao Bagadi
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  5. Arvind Mathur
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by RAA, and SKC: the first draft of the manuscript was written by RG and MB, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Muralidhararao Bagadi.

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Arulraj, R.A., Gajjela, R., Chauthe, S.K. et al. High-Throughput GC-FID Method for the Determination of Residual Solvents in Early-Phase Drug Discovery Samples. Chromatographia 85, 497–506 (2022). https://doi.org/10.1007/s10337-022-04157-9

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  • DOI: https://doi.org/10.1007/s10337-022-04157-9

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