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Validation of an LC-MS/MS method for the quantitative determination of mavoglurant (AFQ056) in human plasma

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Abstract

A simple, sensitive, and selective liquid chromatography/tandem mass spectrometry method was validated for the identification and quantification of mavoglurant (AFQ056) in human plasma. The chromatographic separation was performed using a Cosmosil 5 C18 (150 × 4.6 mm, 5 μm) column at 40 ± 0.5 °C with a mobile phase consisting of acetic acid in water (0.1 %, v/v)/methanol (10:90, v/v) with a flow rate of 1.0 mL/min followed by quantification with tandem mass spectrometry, operating with electrospray ionization in positive ion mode and applying multiple reaction monitoring. The validated method described in this paper presents high absolute recovery with precision and accuracy meeting the acceptance criteria. The method was precise and accurate for 2- and 10-fold dilution of samples. The method was validated using sodium heparin as specific anticoagulant, and the anticoagulant effect was tested by lithium heparin and K3EDTA. The method was successfully cross-validated between two bioanalytical sites. The method was specific for mavoglurant within the given criteria for acceptance (apparent peak area at the retention time of mavoglurant in zero samples was less than 20 % compared with the mean peak area at LLOQ) in human plasma. The method was fully validated for the quantitative determination of mavoglurant in human plasma between the range of 2.00 and 2,500 ng/mL.

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Acknowledgments

The authors acknowledge the assistance of Phaninatha Sarma Ayalavajjala, Novartis Healthcare Private Limited, in the development of this manuscript.

Conflict of interest statement

The authors have no conflicts of interest to disclose.

Disclosure

This study was funded by Novartis Pharma AG.

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Authors and Affiliations

  1. Drug Metabolism and Pharmacokinetics, Novartis Institutes for BioMedical Research, Novartis Pharma AG., Fabrikstrasse 14, 3.02, 4056, Basel, Switzerland

    Annamaria Jakab

  2. Drug Metabolism and Pharmacokinetics, Novartis Institutes for BioMedical Research, Fabrikstrasse 14, 4056, Basel, Switzerland

    Serge Winter, Marc Raccuglia, Swati Dumitras, Ralph Woessner & Olivier Kretz

  3. Bioanalytics Division, Drug Metabolism and Pharmacokinetics, Novartis Institutes for BioMedical Research, Fabrikstrasse 14, 4056, Basel, Switzerland

    Frank Picard

  4. Veeda Clinical Research Pvt. Ltd, Shivalik Plaza-A, Near I.I.M., Ambawadi, Ahmedabad, 380015, India

    Sanket Mistry, Jayraj Chudasama & Swati Guttikar

Authors
  1. Annamaria Jakab
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  2. Serge Winter
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  3. Marc Raccuglia
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  4. Frank Picard
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  5. Swati Dumitras
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  6. Ralph Woessner
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  7. Sanket Mistry
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  8. Jayraj Chudasama
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  9. Swati Guttikar
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  10. Olivier Kretz
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Correspondence to Annamaria Jakab.

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Jakab, A., Winter, S., Raccuglia, M. et al. Validation of an LC-MS/MS method for the quantitative determination of mavoglurant (AFQ056) in human plasma. Anal Bioanal Chem 405, 215–223 (2013). https://doi.org/10.1007/s00216-012-6456-y

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  • DOI: https://doi.org/10.1007/s00216-012-6456-y

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