Plasma and urinary concentrations of trimetoquinol by LC-MS-MS following intravenous and intra-tracheal administration to horses with heaves.
Abstract: Trimetoquinol (TMQ) is a very potent and fast acting bronchodilator in horses with heaves. This study assessed the plasma and urinary concentrations of TMQ in horses with heaves following administration via the intravenous (IV, 0.2 microg/kg) and intra-tracheal (IT, 2 microg/kg) routes. TMQ was administered to six horses affected with heaves (RAO - Recurrent Airway Obstruction, used interchangeably) by the above routes and plasma and urine samples collected and stored at -20 degrees C until analyzed. Solid Phase Extraction (SPE) of TMQ was followed by highly sensitive ESI(+)-LC-MS-MS (ElectroSpray Ionization, positive mode - Liquid Chromatography - Mass Spectrometry - Mass Spectrometry); with a Limit of Detection (LOD) estimated at 1 pg/mL. Following IV administration, TMQ plasma levels peaked at 1 min at 707 pg/mL, and at 9 min at 306 pg/mL following IT administration. Our results show that TMQ plasma concentrations decline rapidly following IV administration, which is consistent with the fast onset and short duration of TMQ effect that was observed in our previous studies. On the other hand, IT administration showed a very unique plasma concentration pattern. From a regulatory standpoint, the current available TMQ ELISA kit was also used in an attempt to detect TMQ from the plasma and urine samples. We report that the ELISA kit was unable to detect TMQ from any of the samples generated in these studies.
Publication Date: 2008-11-13 PubMed ID: 19000271DOI: 10.1111/j.1365-2885.2008.00984.xGoogle Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
- Biochemistry
- Bronchodilation
- Clinical Study
- Disease Treatment
- Drug
- Equine Health
- High-performance Liquid Chromatography (HPLC)
- Horses
- Intravenous Administration
- Laboratory Methods
- Metabolites
- Pharmacodynamics
- Pharmacokinetics
- Plasma
- Recurrent Airway Obstruction
- Respiratory Health
- Urine Analysis
- Veterinary Medicine
- Veterinary Research
Summary
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The research article focuses on the study of plasma and urinary concentrations of Trimetoquinol in horses afflicted with heaves, following intravenous and intra-tracheal administration. The researchers used advanced analytical methods, including LC-MS-MS, to quantify Trimetoquinol levels, and found discrepancies between the results and those from an available ELISA kit.
Subject and Purpose of the Study
- This research focuses on determining the concentration of Trimetoquinol (TMQ), a potent bronchodilator, in the plasma and urine of horses experiencing heaves, also known as Recurrent Airway Obstruction (RAO).
- The objective of this study is to understand how TMQ concentrations change over time when applied either intravenously (IV) or intra-tracheally (IT) in horses, which can provide valuable insights into the drug’s effective dosage and its pharmacokinetics.
Experimental Procedure
- TMQ was administered to six horses suffering from heaves via two routes — intravenously (0.2 microg/kg) and intra-tracheally (2 microg/kg).
- Post-administration, plasma and urine samples were collected from these horses and stored at a temperature of -20 degrees Celsius until analyzed.
- To isolate and quantify TMQ, Solid Phase Extraction was performed, followed by ElectroSpray Ionization, positive mode – Liquid Chromatography – Mass Spectrometry – Mass Spectrometry (ESI(+)-LC-MS-MS).
- The researchers estimated the Limit of Detection (LOD) at 1 pg/mL. The LOD is a measurement of the minimum amount of TMQ that can be detected accurately using their analytical methods.
Outcomes and Findings
- The experimenting group noted that high plasma concentrations of TMQ were registered as early as 1 min into IV administration (707 pg/mL), exhibiting rapid absorption of the drug.
- However, the concentration rapidly declined, aligning with prior observations of TMQ’s fast onset and short-acting duration.
- In contrast, after IT administration, the peak plasma levels of 306 pg/mL were reached slightly later, at 9 min.
- In an attempt to also detect TMQ from the plasma and urine samples using an existing ELISA kit, the researchers found that the kit was unsuccessful in identifying TMQ from any samples.
Implications of the Study
- The inability of the ELISA kit to detect TMQ raises questions regarding the suitability and accuracy of using such a kit for studying and monitoring TMQ concentrations.
- The study provides a greater understanding of TMQ’s pharmacokinetic profile, which is vital for determining the optimal dosing strategy for horses suffering from heaves. This result underscores the need for further optimization of TMQ’s administration in the medical field.
Cite This Article
APA
Camargo FC, Robinson NE, Dirikolu L, Berney C, Eberhart S, Derksen FJ, Lehner AF, May J, Hughes C, Tobin T.
(2008).
Plasma and urinary concentrations of trimetoquinol by LC-MS-MS following intravenous and intra-tracheal administration to horses with heaves.
J Vet Pharmacol Ther, 31(6), 501-510.
https://doi.org/10.1111/j.1365-2885.2008.00984.x Publication
Researcher Affiliations
- Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, USA. fernanda.camargo@uky.edu
MeSH Terms
- Airway Obstruction / drug therapy
- Airway Obstruction / veterinary
- Animals
- Bronchodilator Agents / blood
- Bronchodilator Agents / therapeutic use
- Bronchodilator Agents / urine
- Chromatography, Liquid
- Female
- Horses
- Injections, Intravenous
- Intubation, Intratracheal
- Male
- Mass Spectrometry / methods
- Tretoquinol / blood
- Tretoquinol / therapeutic use
- Tretoquinol / urine
Citations
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