Complementary biomarker detection for bisphosphonate use in racehorses
- Publisher:
- Elsevier
- Publication Type:
- Journal Article
- Citation:
- Toxicologie Analytique et Clinique, 2022, 34, (3), pp. s23-s24
- Issue Date:
- 2022-09
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| 20626869_10460033750005671.pdf | 147.78 kB |
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Aim Determining the use of off-label bisphosphonates (BPs) in young horses ( 4 years old) is of interest due to the threat to racing integrity and welfare associated with this class of drugs that have the potential to manipulate bone structure. The analysis of BPs in biological matrices is challenging by liquid chromatography coupled to mass spectrometry (LC-MS/MS) and alternative sample preparation approaches are needed to detect their misuse in racehorses. There are currently two classes of BPs: non-nitrogen and nitrogen-containing with each having a distinct mode of action. Currently two non-nitrogenous based BPs are available for use in horses, tiludronic acid (or tiludronate) and chlodronate for the treatment of navicular syndrome (Mitchell et al. BMC Veterinary Research 2019;15(1):211) in horses over the age of 4. There is, however, evidence that BPs can persist in the bone for several years after administration since they can form hydroxyapatite crystals prior to being fully absorbed by active osteoclasts where full inhibitory action is performed (Riggs et al. Equine veterinary journal 2021;53(6):1287–1295). Therefore, with this prolonged detection time for the BPs, it is necessary to investigate whether the use of metabolomic biomarkers can provide a complementary method for the detection of their misuse. The aim of this research was to develop a biomarker approach for complementary direct detection of bisphosphonate drugs in equine plasma. Method BPs are hydrophilic therefore the targeted detection of tiludronic acid in equine plasma required an orthogonal solid phase extraction (SPE) method using both a polymeric reversed-phase sorbent and a weak anion exchange cartridge prior to derivatisation using trimethyl orthoacetate and reverse LC-MS/MS. Endogenous lipids and corticosteroids in equine plasma were detected after protein precipitation and SPE with a polymeric reverse phase cartridge prior to liquid chromatography high-resolution mass spectrometry. Da
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