Acepromazine pharmacokinetics: A forensic perspective.

Fiona Schneiders, Glenys Noble, Raymond C. Boston, Anthony J. Dunstan, Martin Sillence, Andrew R. McKinney

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Acepromazine (ACP) is a useful therapeutic drug, but is a prohibited substance in competition horses. The illicit use of ACP is difficult to detect due to its rapid metabolism, so this study investigated the ACP metabolite 2-(1-hydroxyethyl)promazine sulphoxide (HEPS) as a potential forensic marker. Acepromazine maleate, equivalent to 30 mg of ACP, was given IV to 12 racing-bred geldings. Blood and urine were collected for 7 days post-administration and analysed for ACP and HEPS by liquid chromatography'mass spectrometry (LC'MS).Acepromazine was quantifiable in plasma for up to 3 h with little reaching the urine unmodified. Similar to previous studies, there was wide variation in the distribution and metabolism of ACP. The metabolite HEPS was quantifiable for up to 24 h in plasma and 144 h in urine. The metabolism of ACP to HEPS was fast and erratic, so the early phase of the HEPS emergence could not be modelled directly, but was assumed to be similar to the rate of disappearance of ACP. However, the relationship between peak plasma HEPS and the y-intercept of the kinetic model was strong (P = 0.001, r2 = 0.72), allowing accurate determination of the formation pharmacokinetics of HEPS. Due to its rapid metabolism, testing of forensic samples for the parent drug is redundant with IV administration. The relatively long half-life of HEPS and its stable behaviour beyond the initial phase make it a valuable indicator of ACP use, and by determining the urine-to-plasma concentration ratios for HEPS, the approximate dose of ACP administration may be estimated.
Original languageEnglish
Pages (from-to)48-54
Number of pages7
JournalVeterinary Journal
Volume194
Issue number1
DOIs
Publication statusPublished - Oct 2012

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Acepromazine
acepromazine
promazine
Promazine
pharmacokinetics
Pharmacokinetics
urine
Urine
metabolism
forensic sciences
metabolites
maleates
drugs
geldings
intravenous injection
Liquid Chromatography
Pharmaceutical Preparations
liquid chromatography
Horses
half life

Cite this

Schneiders, F., Noble, G., Boston, R. C., Dunstan, A. J., Sillence, M., & McKinney, A. R. (2012). Acepromazine pharmacokinetics: A forensic perspective. Veterinary Journal, 194(1), 48-54. https://doi.org/10.1016/j.tvjl.2012.03.017
Schneiders, Fiona ; Noble, Glenys ; Boston, Raymond C. ; Dunstan, Anthony J. ; Sillence, Martin ; McKinney, Andrew R. / Acepromazine pharmacokinetics : A forensic perspective. In: Veterinary Journal. 2012 ; Vol. 194, No. 1. pp. 48-54.
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Schneiders, F, Noble, G, Boston, RC, Dunstan, AJ, Sillence, M & McKinney, AR 2012, 'Acepromazine pharmacokinetics: A forensic perspective.', Veterinary Journal, vol. 194, no. 1, pp. 48-54. https://doi.org/10.1016/j.tvjl.2012.03.017

Acepromazine pharmacokinetics : A forensic perspective. / Schneiders, Fiona; Noble, Glenys; Boston, Raymond C.; Dunstan, Anthony J.; Sillence, Martin; McKinney, Andrew R.

In: Veterinary Journal, Vol. 194, No. 1, 10.2012, p. 48-54.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Acepromazine pharmacokinetics

T2 - A forensic perspective.

AU - Schneiders, Fiona

AU - Noble, Glenys

AU - Boston, Raymond C.

AU - Dunstan, Anthony J.

AU - Sillence, Martin

AU - McKinney, Andrew R.

N1 - Imported on 12 Apr 2017 - DigiTool details were: month (773h) = October, 2012; Journal title (773t) = The Veterinary Journal. ISSNs: 1090-0233;

PY - 2012/10

Y1 - 2012/10

N2 - Acepromazine (ACP) is a useful therapeutic drug, but is a prohibited substance in competition horses. The illicit use of ACP is difficult to detect due to its rapid metabolism, so this study investigated the ACP metabolite 2-(1-hydroxyethyl)promazine sulphoxide (HEPS) as a potential forensic marker. Acepromazine maleate, equivalent to 30 mg of ACP, was given IV to 12 racing-bred geldings. Blood and urine were collected for 7 days post-administration and analysed for ACP and HEPS by liquid chromatography'mass spectrometry (LC'MS).Acepromazine was quantifiable in plasma for up to 3 h with little reaching the urine unmodified. Similar to previous studies, there was wide variation in the distribution and metabolism of ACP. The metabolite HEPS was quantifiable for up to 24 h in plasma and 144 h in urine. The metabolism of ACP to HEPS was fast and erratic, so the early phase of the HEPS emergence could not be modelled directly, but was assumed to be similar to the rate of disappearance of ACP. However, the relationship between peak plasma HEPS and the y-intercept of the kinetic model was strong (P = 0.001, r2 = 0.72), allowing accurate determination of the formation pharmacokinetics of HEPS. Due to its rapid metabolism, testing of forensic samples for the parent drug is redundant with IV administration. The relatively long half-life of HEPS and its stable behaviour beyond the initial phase make it a valuable indicator of ACP use, and by determining the urine-to-plasma concentration ratios for HEPS, the approximate dose of ACP administration may be estimated.

AB - Acepromazine (ACP) is a useful therapeutic drug, but is a prohibited substance in competition horses. The illicit use of ACP is difficult to detect due to its rapid metabolism, so this study investigated the ACP metabolite 2-(1-hydroxyethyl)promazine sulphoxide (HEPS) as a potential forensic marker. Acepromazine maleate, equivalent to 30 mg of ACP, was given IV to 12 racing-bred geldings. Blood and urine were collected for 7 days post-administration and analysed for ACP and HEPS by liquid chromatography'mass spectrometry (LC'MS).Acepromazine was quantifiable in plasma for up to 3 h with little reaching the urine unmodified. Similar to previous studies, there was wide variation in the distribution and metabolism of ACP. The metabolite HEPS was quantifiable for up to 24 h in plasma and 144 h in urine. The metabolism of ACP to HEPS was fast and erratic, so the early phase of the HEPS emergence could not be modelled directly, but was assumed to be similar to the rate of disappearance of ACP. However, the relationship between peak plasma HEPS and the y-intercept of the kinetic model was strong (P = 0.001, r2 = 0.72), allowing accurate determination of the formation pharmacokinetics of HEPS. Due to its rapid metabolism, testing of forensic samples for the parent drug is redundant with IV administration. The relatively long half-life of HEPS and its stable behaviour beyond the initial phase make it a valuable indicator of ACP use, and by determining the urine-to-plasma concentration ratios for HEPS, the approximate dose of ACP administration may be estimated.

KW - Drug metabolism

KW - Equine

KW - Excretion time

KW - Sedative

U2 - 10.1016/j.tvjl.2012.03.017

DO - 10.1016/j.tvjl.2012.03.017

M3 - Article

VL - 194

SP - 48

EP - 54

JO - The Veterinary Journal

JF - The Veterinary Journal

SN - 1090-0233

IS - 1

ER -

Schneiders F, Noble G, Boston RC, Dunstan AJ, Sillence M, McKinney AR. Acepromazine pharmacokinetics: A forensic perspective. Veterinary Journal. 2012 Oct;194(1):48-54. https://doi.org/10.1016/j.tvjl.2012.03.017