HFL Sport Science Inc.

Lexington, KY, United States

HFL Sport Science Inc.

Lexington, KY, United States
SEARCH FILTERS
Time filter
Source Type

Rumpler M.J.,University of Florida | Colahan P.,University of Florida | Sams R.A.,University of Florida | Sams R.A.,HFL Sport Science Inc.
Journal of Veterinary Pharmacology and Therapeutics | Year: 2014

A simple LC/MSMS method has been developed and fully validated to determine concentrations and characterize the concentration vs. time course of methocarbamol (MCBL) and guaifenesin (GGE) in plasma after a single intravenous dose and multiple oral dose administrations of MCBL to conditioned Thoroughbred horses. The plasma concentration-time profiles for MCBL after a single intravenous dose of 15 mg/kg of MCBL were best described by a three-compartment model. Mean extrapolated peak (C0) plasma concentrations were 23.2 (±5.93) μg/mL. Terminal half-life, volume of distribution at steady-state, mean residence time, and systemic clearance were characterized by a median (range) of 2.96 (2.46-4.71) h, 1.05 (0.943-1.21) L/kg, 1.98 (1.45-2.51) h, and 8.99 (6.68-10.8) mL/min/kg, respectively. Oral dose of MCBL was characterized by a median (range) terminal half-life, mean transit time, mean absorption time, and apparent oral clearance of 2.89 (2.21-4.88) h, 2.67 (1.80-2.87) h, 0.410 (0.350-0.770) h, and 16.5 (13.0-20) mL/min/kg. Bioavailability of orally administered MCBL was characterized by a median (range) of 54.4 (43.2-72.8)%. Guaifenesin plasma concentrations were below the limit of detection in all samples collected after the single intravenous dose of MCBL whereas they were detected for up to 24 h after the last dose of the multiple-dose oral regimen. This difference may be attributed to first-pass metabolism of MCBL to GGE after oral administration and may provide a means of differentiating the two routes of administration. © 2013 John Wiley & Sons Ltd.


Knych H.K.,University of California at Davis | Corado C.R.,University of California at Davis | Mckemie D.S.,University of California at Davis | Scholtz E.,University of California at Davis | Sams R.,HFL Sport Science Inc.
Journal of Veterinary Pharmacology and Therapeutics | Year: 2013

Tramadol is a synthetic opioid used in human medicine, and to a lesser extent in veterinary medicine, for the treatment of both acute and chronic pain. In humans, the analgesic effects are owing to the actions of both the parent compound and an active metabolite (M1). The goal of the current study was to extend current knowledge of the pharmacokinetics of tramadol and M1 following oral administration of three doses of tramadol to horses. A total of nine healthy adult horses received a single oral administration of 3, 6, and 9 mg/kg of tramadol via nasogastric tube. Blood samples were collected at time 0 and at various times up to 96 h after drug administration. Urine samples were collected until 120 h after administration. Plasma and urine samples were analyzed using liquid chromatography-mass spectrometry, and the resulting data analyzed using noncompartmental analysis. For the 3, 6, and 9 mg/kg dose groups, Cmax, Tmax, and the t1/2λ were 43.1, 90.7, and 218 ng/mL, 0.750, 2.0, and 1.5 h and 2.14, 2.25, and 2.39 h, respectively. While tramadol and M1 plasma concentrations within the analgesic range for humans were attained in the 3 and 6 mg/kg dose group, these concentrations were at the lower end of the analgesic range and were only transiently maintained. Furthermore, until effective analgesic plasma concentrations have been established in horses, tramadol should be cautiously recommended for control of pain in horses. No significant undesirable behavioral or physiologic effects were noted at any of the doses administered. © 2012 John Wiley & Sons Ltd.


Rumpler M.J.,Florida College | Kandala B.,Florida College | Vickroy T.W.,Florida College | Hochhaus G.,Florida College | Sams R.A.,HFL Sport Science Inc.
Journal of Veterinary Pharmacology and Therapeutics | Year: 2014

Glycopyrrolate (GLY) is an antimuscarinic agent that is used in humans and domestic animals primarily to reduce respiratory tract secretions during anesthesia and to reverse intra-operative bradycardia. Although GLY is used routinely in veterinary patients, there is limited information regarding its pharmacokinetic (PK) and pharmacodynamic (PD) properties in domestic animals, and an improved understanding of the plasma concentration-effect relationship in racehorses is warranted. To accomplish this, we characterize the pharmacokinetic-pharmacodynamic (PK-PD) actions of GLY during and after a 2-h constant-rate intravenous infusion (4 μg/kg/h) and evaluate potential PK-PD models for cardiac stimulation in adult horses. Measurements of plasma GLY concentrations, heart and respiration rates, and frequency of bowel movements were performed in six Thoroughbred horses. The time course for GLY disposition in plasma followed a tri-exponential equation characterized by rapid disappearance of GLY from blood followed by a prolonged terminal phase. Physiological monitoring revealed significant (P < 0.01) increases in heart (>70 bpm) and respiratory rates accompanied by a marked and sustained delay in the frequency of bowel movements (1.1 ± 0.2 h [saline group] vs. 6.0 ± 2.0 h [GLY group]). Two of six horses showed signs of colic during the 8-h observation period after the end of the GLY infusion, but were treated and recovered without further complications. The relationship between plasma GLY concentration and heart rate exhibited counterclockwise hysteresis that was adequately described using an effect compartment. © 2013 John Wiley & Sons Ltd.


Rumpler M.J.,University of Florida | Colahan P.,University of Florida | Sams R.A.,University of Florida | Sams R.A.,HFL Sport Science Inc.
Journal of Veterinary Pharmacology and Therapeutics | Year: 2014

The disposition of plasma glycopyrrolate (GLY) is characterized by a three-compartment pharmacokinetic model after a 1-mg bolus intravenous dose to Standardbred horses. The median (range) plasma clearance (Clp), volume of distribution of the central compartment (V1), volume of distribution at steady-state (Vss), and area under the plasma concentration-time curve (AUC0-inf) were 16.7 (13.6-21.7) mL/min/kg, 0.167 (0.103-0.215) L/kg, 3.69 (0.640-38.73) L/kg, and 2.58 (2.28-2.88) ng*h/mL, respectively. Renal clearance of GLY was characterized by a median (range) of 2.65 (1.92-3.59) mL/min/kg and represented approximately 11.3-24.7% of the total plasma clearance. As a result of these studies, we conclude that the majority of GLY is cleared through hepatic mechanisms because of the limited extent of renal clearance of GLY and absence of plasma esterase activity on GLY metabolism. Although the disposition of GLY after intravenous administration to Standardbred horses was similar to that in Thoroughbred horses, differences in some pharmacokinetic parameter estimates were evident. Such differences could be attributed to breed differences or study conditions. The research could provide valuable data to support regulatory guidelines for GLY in Standardbred horses. © 2013 John Wiley & Sons Ltd.


Rumpler M.J.,University of Florida | Sams R.A.,University of Florida | Sams R.A.,HFL Sport Science Inc. | Colahan P.,University of Florida
Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences | Year: 2012

We describe a validated, rapid, sensitive, and specific UHPLC-MS/MS method to detect and quantify glycopyrrolate in 0.5. mL of horse urine. Further, we investigated the elimination of glycopyrrolate in urine after both intravenous and oral administration of clinically relevant doses to Thoroughbred horses. Quantification was performed by weighted, linear regression analysis using a deuterated analogue of glycopyrrolate as internal standard (IS). The method was characterized by a linear range of 5-2500. pg/mL, a lower limit of quantification of 5. pg/mL and a limit of detection of 1. pg/mL. The intra and inter-batch imprecisions were <10% RSD and accuracy of the method ranged between 94 and 104%. Glycopyrrolate remained detectable in urine samples collected through 168. h after intravenous administration and through 24. h after oral administration. Analytical method validation requirements for linearity, specificity, precision, accuracy, stability, dilution integrity, matrix effect, and ruggedness have been fulfilled. The urine method described in this report is simple and efficient and is the first reported method with sufficient sensitivity, accuracy, and precision to regulate the use of glycopyrrolate in urine samples collected more than one day after dosing of horses. Urine to plasma glycopyrrolate concentration ratios were calculated and were approximately 100:1 in samples collected from 24. h through the end of sample collection. © 2012 Elsevier B.V.


Hudson S.,HFL Sport Science Ltd | Ramsey J.,St George's, University of London
Drug Testing and Analysis | Year: 2011

In late 2008, several synthetic cannabinoids were detected in herbal smoking mixtures. Typical of these products were 'Spice Gold', 'Spice Silver' and 'Yucatan Fire', but many other products have since appeared. The analytes detected, such as JWH-018 and CP47,497 are experimental compounds, some of which were never designed for human use. Both scientific and anecdotal evidence suggest that these compounds are more potent than traditional cannabis and are being widely used. As a result, authorities around the world are now beginning to control them by either naming individual compounds or using generic legislation. This, however, is easier said than done as the synthetic cannabinoids detected are constantly changing in attempts by manufacturers to evade legislation. This paper includes background information in the style of a brief monograph, as an aid to rapidly understanding the pharmacological aspects of these compounds in the forensic context, and then presents a comprehensive set of data, obtained from analysis of purchased products by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). © 2011 John Wiley & Sons, Ltd.


Fenwick S.J.,HFL Sport Science Ltd. | Scarth J.P.,HFL Sport Science Ltd.
Drug Testing and Analysis | Year: 2011

Within horseracing, the detection of prohibited substance doping often requires urine analysis; hence, it is necessary to understand the metabolism of the drugs in question. Here, the previously unknown equine metabolism of eight sedatives is reported in order to provide information on target metabolites for use in doping control. Phase I metabolite information was provided by incubation with equine liver S9 fraction. In vitro techniques were chosen in order to reduce the ethical and financial issues surrounding the study of so many compounds, none of which are licensed for use in horses in the UK. Several metabolites of each drug were identified using liquid chromatography-high resolution mass spectrometric (LC-HRMS) analysis on an LTQ-Orbitrap. Further structural information was obtained by tandem mass spectrometry (MS/MS) analysis; allowing postulation of the structure of some of the most abundant in vitro metabolites. The most abundant metabolites of alpidem, etifoxine, indiplon, tiletamine, zaleplon, zolazepam, zolpidem, and zopiclone related to hydroxylation/N-oxidation, deethylation, demethylation, deethylation, hydroxylation/N-oxidation, demethylation, hydroxylation/N-oxidation and hydroxylation/N-oxidation, respectively. In many cases, further work would be required to fully elucidate the precise positioning of the functional groups involved. The results of this study provide metabolite information that can be used to enhance equine anti-doping screening methods. However, the in vitro metabolites identified are at present only a prediction of those that may occur in vivo. In the future, any positive findings of these drugs and/or their metabolites in horse urine samples could help validate these findings and/or refine the choice of target metabolites. © 2011 John Wiley & Sons, Ltd.


PubMed | HFL Sport Science Ltd
Type: Journal Article | Journal: Drug testing and analysis | Year: 2011

Within horseracing, the detection of prohibited substance doping often requires urine analysis; hence, it is necessary to understand the metabolism of the drugs in question. Here, the previously unknown equine metabolism of eight sedatives is reported in order to provide information on target metabolites for use in doping control. Phase I metabolite information was provided by incubation with equine liver S9 fraction. In vitro techniques were chosen in order to reduce the ethical and financial issues surrounding the study of so many compounds, none of which are licensed for use in horses in the UK. Several metabolites of each drug were identified using liquid chromatography-high resolution mass spectrometric (LC-HRMS) analysis on an LTQ-Orbitrap. Further structural information was obtained by tandem mass spectrometry (MS/MS) analysis; allowing postulation of the structure of some of the most abundant in vitro metabolites. The most abundant metabolites of alpidem, etifoxine, indiplon, tiletamine, zaleplon, zolazepam, zolpidem, and zopiclone related to hydroxylation/N-oxidation, deethylation, demethylation, deethylation, hydroxylation/N-oxidation, demethylation, hydroxylation/N-oxidation and hydroxylation/N-oxidation, respectively. In many cases, further work would be required to fully elucidate the precise positioning of the functional groups involved. The results of this study provide metabolite information that can be used to enhance equine anti-doping screening methods. However, the in vitro metabolites identified are at present only a prediction of those that may occur in vivo. In the future, any positive findings of these drugs and/or their metabolites in horse urine samples could help validate these findings and/or refine the choice of target metabolites.


PubMed | HFL Sport Science Ltd
Type: Journal Article | Journal: Drug testing and analysis | Year: 2011

In late 2008, several synthetic cannabinoids were detected in herbal smoking mixtures. Typical of these products were Spice Gold, Spice Silver and Yucatan Fire, but many other products have since appeared. The analytes detected, such as JWH-018 and CP47,497 are experimental compounds, some of which were never designed for human use. Both scientific and anecdotal evidence suggest that these compounds are more potent than traditional cannabis and are being widely used. As a result, authorities around the world are now beginning to control them by either naming individual compounds or using generic legislation. This, however, is easier said than done as the synthetic cannabinoids detected are constantly changing in attempts by manufacturers to evade legislation. This paper includes background information in the style of a brief monograph, as an aid to rapidly understanding the pharmacological aspects of these compounds in the forensic context, and then presents a comprehensive set of data, obtained from analysis of purchased products by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Loading HFL Sport Science Inc. collaborators
Loading HFL Sport Science Inc. collaborators