Evaluation of tramadol and its main metabolites in horse plasma by high-performance liquid chromatography/fluorescence and liquid chromatography/electrospray ionization tandem mass spectrometry techniques.
Abstract: Tramadol is a centrally acting analgesic drug that has been used clinically for the last two decades to treat pain in humans. The clinical response of tramadol is strictly correlated to its metabolism, because of the different analgesic activity of its metabolites. O-Desmethyltramadol (M1), its major active metabolite, is 200 times more potent at the micro-receptor than the parent drug. In recent years tramadol has been widely introduced in veterinary medicine but its use has been questioned in some species. The aim of the present study was to develop a new sensible method to detect the whole metabolic profile of the drug in horses, through plasma analyses by high-performance liquid chromatography (HPLC) coupled with fluorimetric (FL) and photodiode array electrospray ionization mass spectrometric (PDA-ESI-MS) detection, after its sustained release by oral administration (5 mg/kg). In HPLC/FL experiments the comparison of the horse plasma chromatogram profile with that of a standard mixture suggested the identification of the major peaks as tramadol and its metabolites M1 and N,O-desmethyltramadol (M5). LC/PDA-ESI-MS/MS analysis confirmed the results obtained by HPLC/FL and also provided the identification of two more metabolites, N-desmethyltramadol (M2), and N,N-didesmethyltramadol (M3). Another metabolite, M6, was also detected and identified. The present findings demonstrate the usefulness and the advantage of LC/ESI-MS/MS techniques in a search for tramadol metabolites in horse plasma samples.
Copyright (c) 2008 John Wiley & Sons, Ltd.
Publication Date: 2008-12-17 PubMed ID: 19072864DOI: 10.1002/rcm.3870Google Scholar: Lookup
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Summary
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This research article explores a new method to detect the metabolic profile of the drug tramadol in horses through plasma analysis by using high-performance liquid chromatography. The method showed the usefulness of utilizing liquid chromatography/electrospray ionization tandem mass spectrometry techniques in tracking tramadol metabolites in horse plasma samples.
Objective
The overarching goal of this study was to develop a new sensitive method that can detect the complete metabolic profile of tramadol in horses after it has been orally administered.
The Significance of Tramadol and Its Metabolites
- The research highlights tramadol, a drug used for pain relief in humans and animals, drawing attention to how its analgesic activity is tightly linked to its metabolism.
- The major active metabolite of tramadol, O-Desmethyltramadol (M1), is identified to have 200 times more potency at the micro-receptor than the parent drug.
- The paper narrates how the drug’s use in veterinary medicine has been met with some scrutiny because its effectiveness can vary across different species.
Implemented Method and Results
- The researchers implemented high-performance liquid chromatography (HPLC), coupled with fluorimetric (FL) and photodiode array electrospray ionization mass spectrometric (PDA-ESI-MS) detection methods, to analyze horse plasma after the oral administration of 5 mg/kg tramadol.
- The results indicated the presence of tramadol and its metabolites M1 and N,O-desmethyltramadol (M5) using HPLC/FL experiments.
- Further analysis through LC/PDA-ESI-MS/MS confirmed the presence of two more metabolites, N-desmethyltramadol (M2), and N,N-didesmethyltramadol (M3). An additional metabolite, M6, was also detected and identified.
Conclusions
- This study provides valuable insights into the metabolic profile of tramadol in horses.
- The researchers concluded that LC/ESI-MS/MS techniques offer a significant advantage when finding tramadol metabolites in horse plasma samples, thereby enhancing our understanding of the drug’s pharmacokinetics in horses.
Cite This Article
APA
De Leo M, Giorgi M, Saccomanni G, Manera C, Braca A.
(2008).
Evaluation of tramadol and its main metabolites in horse plasma by high-performance liquid chromatography/fluorescence and liquid chromatography/electrospray ionization tandem mass spectrometry techniques.
Rapid Commun Mass Spectrom, 23(2), 228-236.
https://doi.org/10.1002/rcm.3870 Publication
Researcher Affiliations
- Dipartimento di Chimica Bioorganica e Biofarmacia, Università di Pisa, Via Bonanno 33, 56126 Pisa, Italy. deleo@farm.unipi.it
MeSH Terms
- Animals
- Blood Chemical Analysis
- Chromatography, High Pressure Liquid / methods
- Chromatography, High Pressure Liquid / veterinary
- Doping in Sports / prevention & control
- Horses / blood
- Illicit Drugs / blood
- Male
- Reproducibility of Results
- Sensitivity and Specificity
- Spectrometry, Fluorescence / methods
- Spectrometry, Fluorescence / veterinary
- Spectrometry, Mass, Electrospray Ionization / methods
- Spectrometry, Mass, Electrospray Ionization / veterinary
- Substance Abuse Detection / methods
- Tramadol / blood
Citations
This article has been cited 4 times.- Luongo G, Previtera L, Ladhari A, Fabio GD, Zarrelli A. Peracetic Acid vs. Sodium Hypochlorite: Degradation and Transformation of Drugs in Wastewater.. Molecules 2020 May 13;25(10).
- Nagaraju P, Kodali B, Datla PV, Kovvasu SP. LC-MS/MS Quantification of Tramadol and Gabapentin Utilizing Solid Phase Extraction.. Int J Anal Chem 2018;2018:1605950.
- Zhou X, Liu J. Fluorescence detection of tramadol in healthy Chinese volunteers by high-performance liquid chromatography and bioequivalence assessment.. Drug Des Devel Ther 2015;9:1225-31.
- Carregaro AB, Freitas GC, Ribeiro MH, Xavier NV, Dória RG. Physiological and analgesic effects of continuous-rate infusion of morphine, butorphanol, tramadol or methadone in horses with lipopolysaccharide (LPS)-induced carpal synovitis.. BMC Vet Res 2014 Dec 21;10:966.
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