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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Greaves, Ronda / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter


IMPACT FACTOR 2018: 3.638

CiteScore 2018: 2.44

SCImago Journal Rank (SJR) 2018: 1.191
Source Normalized Impact per Paper (SNIP) 2018: 1.205

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1437-4331
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Validation according to European and American regulatory agencies guidelines of an LC-MS/MS method for the quantification of free and total ropivacaine in human plasma

Elodie Lamy
  • Plateforme de spectrométrie de masse MasSpecLab, INSERM UMR 1173, UFR Simone Veil – Santé, Université Versailles Saint Quentin, Université Paris Saclay, Montigny le Bretonneux, France
  • Other articles by this author:
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/ Fanta Fall
  • Plateforme de spectrométrie de masse MasSpecLab, INSERM UMR 1173, UFR Simone Veil – Santé, Université Versailles Saint Quentin, Université Paris Saclay, Montigny le Bretonneux, France
  • Other articles by this author:
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/ Lisa Boigne
  • Plateforme de spectrométrie de masse MasSpecLab, INSERM UMR 1173, UFR Simone Veil – Santé, Université Versailles Saint Quentin, Université Paris Saclay, Montigny le Bretonneux, France
  • Other articles by this author:
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/ Kirill Gromov / Nicolas Fabresse
  • Plateforme de spectrométrie de masse MasSpecLab, INSERM UMR 1173, UFR Simone Veil – Santé, Université Versailles Saint Quentin, Université Paris Saclay, Montigny le Bretonneux, France
  • Laboratoire de Toxicologie, Hôpital Raymond Poincaré, AP-HP, Garches, France
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/ Stanislas Grassin-DelyleORCID iD: https://orcid.org/0000-0001-5747-4432
  • Corresponding author
  • Plateforme de spectrométrie de masse MasSpecLab, INSERM UMR 1173, UFR Simone Veil – Santé, Université Versailles Saint Quentin, Université Paris Saclay, Montigny le Bretonneux, France
  • Département des maladies respiratoires, Hôpital Foch, Suresnes, France, Phone: +33.1.70.42.94.22
  • orcid.org/0000-0001-5747-4432
  • Email
  • Other articles by this author:
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Published Online: 2019-04-02 | DOI: https://doi.org/10.1515/cclm-2018-1298

Abstract

Background

Ropivacaine is a widely used local anaesthetic drug, highly bound to plasma proteins with a free plasma fraction of about 5%. Therefore, the monitoring of free drug concentration is most relevant to perform pharmacokinetic studies and to understand the drug pharmacokinetic/pharmacodynamic (PK/PD) relationship.

Methods

A high-sensitivity liquid chromatography-tandem mass spectrometry (LC-MS/MS) method using reverse-phase LC and electrospray ionisation mass spectrometry with multiple reaction monitoring (MRM) is described for the quantitation of both free and total ropivacaine in human plasma. Ropivacaine-d7 was used as an internal standard (IS).

Results

The method was validated in the range 0.5–3000 ng/mL, with five levels of QC samples and according to the European Medicine Agency and Food and Drug Administration guidelines. The performance of the method was excellent with a precision in the range 6.2%–14.7%, an accuracy between 93.6% and 113.7% and a coefficient of variation (CV) of the IS-normalised matrix factor below 15%. This suitability of the method for the quantification of free and total ropivacaine in clinical samples was demonstrated with the analysis of samples from patients undergoing knee arthroplasty and receiving a local ropivacaine infiltration.

Conclusions

A method was developed and validated for the quantification of free and total ropivacaine in human plasma and was shown suitable for the analysis of clinical samples.

Keywords: EMA guideline; FDA guideline; free drug concentration; human plasma; liquid chromatography; mass spectrometry; ropivacaine

References

  • 1.

    Hansen TG. Ropivacaine: a pharmacological review. Expert Rev Neurother 2004;4:781–91.CrossrefPubMedGoogle Scholar

  • 2.

    Simpson D, Curran MP, Oldfield V, Keating GM. Ropivacaine: a review of its use in regional anaesthesia and acute pain management. Drugs 2005;65:2675–717.PubMedCrossrefGoogle Scholar

  • 3.

    Zink W, Graf BM. The toxicity of local anesthetics: the place of ropivacaine and levobupivacaine. Curr Opin Anaesthesiol 2008;21:645–50.PubMedCrossrefGoogle Scholar

  • 4.

    Barri T, Trtic-Petrovic T, Karlsson M, Jonsson JA. Characterization of drug-protein binding process by employing equilibrium sampling through hollow-fiber supported liquid membrane and Bjerrum and Scatchard plots. J Pharm Biomed Anal 2008;48:49–56.PubMedCrossrefWeb of ScienceGoogle Scholar

  • 5.

    Taheri S, Cogswell LP, 3rd, Gent A, Strichartz GR. Hydrophobic and ionic factors in the binding of local anesthetics to the major variant of human alpha1-acid glycoprotein. J Pharmacol Exp Ther 2003;304:71–80.PubMedCrossrefGoogle Scholar

  • 6.

    Lee A, Fagan D, Lamont M, Tucker GT, Halldin M, Scott DB. Disposition kinetics of ropivacaine in humans. Anesth Analg 1989;69:736–8.PubMedGoogle Scholar

  • 7.

    Arvidsson T, Eklund E. Determination of free concentration of ropivacaine and bupivacaine in blood plasma by ultrafiltration and coupled-column liquid chromatography. J Chromatogr B Biomed Appl 1995;668:91–8.CrossrefPubMedGoogle Scholar

  • 8.

    Bergstrom SK, Markides KE. On-line coupling of microdialysis to packed capillary column liquid chromatography-tandem mass spectrometry demonstrated by measurement of free concentrations of ropivacaine and metabolite from spiked plasma samples. J Chromatogr B Analyt Technol Biomed Life Sci 2002;775:79–87.PubMedCrossrefGoogle Scholar

  • 9.

    Abbas M, Ahmad L, Shah Y, Gill M, Watson DG. Development of a method to measure free and bound ropivacaine in human plasma using equilibrium dialysis and hydrophilic interaction chromatography coupled to high resolution mass spectrometry. Talanta 2013;117:60–3.CrossrefWeb of SciencePubMedGoogle Scholar

  • 10.

    Mathieu O, Hillaire-Buys D, Dadure C, Barnay F, Mathieu-Daude JC, Bressolle F. Liquid chromatography-electrospray mass spectrometry determination of free and total concentrations of ropivacaine in human plasma. J Chromatogr B Analyt Technol Biomed Life Sci 2006;831:91–8.CrossrefPubMedGoogle Scholar

  • 11.

    Stumpe M, Morton NS, Watson DG. Determination of free concentrations of ropivacaine and bupivacaine in plasma from neonates using small-scale equilibrium-dialysis followed by liquid chromatography-mass spectrometry. J Chromatogr B Biomed Sci Appl 2000;748:321–30.CrossrefPubMedGoogle Scholar

  • 12.

    Musteata FM. Monitoring free drug concentrations: challenges. Bioanalysis 2011;3:1753–68.PubMedWeb of ScienceCrossrefGoogle Scholar

  • 13.

    Nilsson LB. The bioanalytical challenge of determining unbound concentration and protein binding for drugs. Bioanalysis 2013;5:3033–50.CrossrefPubMedWeb of ScienceGoogle Scholar

  • 14.

    Banker MJ, Clark TH. Plasma/serum protein binding determinations. Curr Drug Metab 2008;9:854–9.CrossrefWeb of SciencePubMedGoogle Scholar

  • 15.

    Buscher B, Laakso S, Mascher H, Pusecker K, Doig M, Dillen L, et al. Bioanalysis for plasma protein binding studies in drug discovery and drug development: views and recommendations of the European Bioanalysis Forum. Bioanalysis 2014;6: 673–82.PubMedCrossrefWeb of ScienceGoogle Scholar

  • 16.

    Brydone AS, Souvatzoglou R, Abbas M, Watson DG, McDonald DA, Gill AM. Ropivacaine plasma levels following high-dose local infiltration analgesia for total knee arthroplasty. Anaesthesia 2015;70:784–90.PubMedCrossrefWeb of ScienceGoogle Scholar

  • 17.

    Gill AM, Scott NB, Abbas M, Watson DG, Place K, McDonald DA. Ropivacaine plasma levels following local infiltration analgesia for primary total hip arthroplasty. Anaesthesia 2014;69:368–73.Web of ScienceCrossrefPubMedGoogle Scholar

About the article

Corresponding author: Stanislas Grassin-Delyle, Plateforme de spectrométrie de masse MasSpecLab, INSERM UMR 1173, UFR Simone Veil – Santé, Université Versailles Saint Quentin, Université Paris Saclay, 2 avenue de la source de la Bièvre, 78180 Montigny le Bretonneux, France


Received: 2018-12-05

Accepted: 2019-03-05

Published Online: 2019-04-02


Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organisation(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.


Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), 20181298, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2018-1298.

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