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Sensitive Determination of Fentanyl in Low-Volume Serum Samples by LC-MS/MS

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  • Theme: Team Science and Education for Pharmaceuticals: the NIPTE Model
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Abstract

Fentanyl is a widely used drug in the management of pain. Present LC-MS/MS methods for analysis of fentanyl require a large volume of serum, but yet the sensitivity was at about 50 pg/mL. Here, we report a modified liquid-liquid extraction method for the analysis of fentanyl in serum. The method is very sensitive with a LLOQ of 5 pg/mL while using only 0.175 mL of serum for analysis. The separation was performed on a Zorbax XDB-C18 column (4.6 × 50 mm, 1.8 μm, 600 bar) using a mobile phase of water: acetonitrile (70:30 v/v) with 0.1% formic acid that was pumped isocratically at a flow rate of 0.5 mL per minute. The calibration curve was found to be linear over a range of 5–10,000 pg/mL. The inter-day and intra-day accuracy and precision were tested using low (20 pg/mL), medium (1000 pg/mL), and high (5000 pg/mL) quality control samples of fentanyl prepared in blank human serum and were within ± 15% of the nominal value. Fentanyl was also found to be stable in various storage and sample preparation conditions, including short-term bench-top storage (for 5 h), freeze-thaw cycling (three cycles), long-term frozen condition (4.5 months at - 70°C), and post-preparative storage (for 48 h).

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Acknowledgements

Authors acknowledge Dr. Timothy Wiedmann, Department of Pharmaceutics, UMN, for critically reading the manuscript.

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Authors and Affiliations

  1. Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, USA

    Suresh Kumar Swaminathan & Karunya K. Kandimalla

  2. The Clinical Pharmacology Analytical Services (CPAS) Laboratory, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, USA

    James Fisher

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  1. Suresh Kumar Swaminathan
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Correspondence to Karunya K. Kandimalla.

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Guest Editors: Ajaz S. Hussain, Kenneth Morris, and Vadim J. Gurvich

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Swaminathan, S.K., Fisher, J. & Kandimalla, K.K. Sensitive Determination of Fentanyl in Low-Volume Serum Samples by LC-MS/MS. AAPS PharmSciTech 19, 2812–2817 (2018). https://doi.org/10.1208/s12249-018-1103-3

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  • DOI: https://doi.org/10.1208/s12249-018-1103-3

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