Validation of a LC-MS/MS method to simultaneously quantify thiafentanil and naltrexone in plasma for pharmacokinetic studies in wildlife.

Thiafentanil is a popular opioid agonist that is fully reversed by administering naltrexone. This agonist-antagonist combination is administered to a wide variety of wildlife species for chemical immobilisation, however plasma concentrations for thiafentanil remain unreported. This report describes a method that was developed and validated using human plasma and cross-validated for the analysis of goat plasma. Samples were extracted using a simple protein precipitation and analysed using LC-MS/MS. The assay was validated over the calibration range 4.38 - 1120 ng/mL for thiafentanil and 15.63 - 4000 ng/mL for naltrexone. The mean inter-day accuracies for QCs prepared in human plasma (n = 18) ranged from 94.8 - 103.8 % for thiafentanil and 94.8 - 95.9 % for naltrexone with corresponding precisions of 3.4 - 7.9 % and 2.8 - 11.4 %, respectively. The mean accuracies for QCs prepared in goat plasma (n = 6) ranged from 89.0 - 100.5 % for thiafentanil and 89.0 - 98.0 % for naltrexone with the associated precisions ranging from 7.1 - 11.6 % and 4.8 - 12.3 %, respectively. Both analytes were stable on bench for six hours and for three freeze-thaw cycles. The impact of heat-inactivation, necessary for the inactivation of potential foot-and-mouth disease, on analyte stability, matrix effect and recovery were evaluated, and a correction factor was established to determine the original analyte concentrations. The method was applied to pharmacokinetic samples collected from goats. The use of goats as a model species provides the first insight into the plasma concentrations of thiafentanil.

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Copyright © 2023. Published by Elsevier B.V.

Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Judith T Christie reports financial support and equipment, drugs, or supplies were provided by Wildlife Pharmaceuticals Pty. Ltd. Liesel Laubscher reports financial support was provided by Wildlife Pharmaceuticals Pty. Ltd. Jacobus P Raath reports financial support was provided by Wildlife Pharmaceuticals Pty. Ltd. Judith T Christie reports a relationship with Wildlife Pharmaceuticals Pty. Ltd. that includes: funding grants. Liesel Laubscher reports a relationship with Wildlife Pharmaceuticals Pty. Ltd. that includes: employment. Jacobus P Raath reports a relationship with Wildlife Pharmaceuticals Pty. Ltd. that includes: employment. Judith T Christie reports financial support for the Murdoch University Strategic Partnership Scholarship was provided by Wildlife Pharmaceuticals Pty Ltd. Liesel Laubscher is employed as the Product Specialist at Wildlife Pharmaceuticals Pty Ltd. Jacobus P Raath is the Managing Director at Wildlife Pharmaceuticals Pty. Ltd.